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At least 541 records · Page 30Linked to original sources
PubMed2004

Differential gene expression of early and late passage retinal pigment epithelial cells.

We examined the gene expression profiles of retinal pigment epithelial (RPE) cells which were aged in vitro by repeated passage. RPE cells from human eyes were cultured to passage 3-5 (early passage) or 19-21 (late passage) and used to study gene expression profiles by cDNA microarray. Results from microarray analysis were further confirmed by real-time PCR. Microarray analysis showed gene expression changes among 588 known genes. The expression levels of 15 genes (2.6%) increased in late passage RPE cells, while 43 genes (7.3%) decreased using a two-fold criterion. These differentially expressed genes encompassed many functional classes. A small number of stress genes, such as clusterin, replication protein A and Ku80, were up-regulated. The down-regulated genes included many enzymes of energy and biomolecule metabolism as well as cell cycle proteins and cell adhesion proteins. Results from real-time PCR were generally consistent with microarray findings. The expression levels of the examined angiogenic factors were either unchanged or down-regulated. Comparing early (p=3-5) and late (p=9-12) passage RPE cells, several categories of differentially expressed genes were identified. However, there was no enhanced expression of known angiogenic factors.

Angiogenesis Inducing Agents↗
PubMed2000

Cell cycle regulation in H(2)O(2)-induced premature senescence of human diploid fibroblasts and regulatory control exerted by the papilloma virus E6 and E7 proteins.

Many biomarkers of replicative senescence appear in stress-induced premature senescence (SIPS) of human diploid fibroblasts (HDFs). The mRNA level of key cell cycle regulators was studied in H(2)O(2)-induced premature senescence of HDFs expressing or not the papillomavirus E6 and E7 proteins, which enhanced, respectively, the proteolysis of p53 and Rb. The CdKI's p21(waf-1) and p16(Ink-4a) were found overexpressed in H(2)O(2)-induced premature senescence, while p19(Ink-4d)and p27(Kip-1) were repressed. The results obtained in E6 HDFs suggest that p21(waf-1) and p16(Ink-4a) overexpressions are p53-independent, while p27(Kip-1) and p19(Ink-4d) down-regulations are p53-dependent.E6 regulated Rb, p130, p53 and p16(Ink-4a) mRNA level in non-stressing conditions, and regulated p130, p107, p53, p19(Ink-4d), p27(Kip-1) mRNA level in SIPS. SIPS modified the E6-mediated regulatory control on p107, p16(Ink-4a), p19(Ink-4d) and p27(Kip-1) mRNA level, when compared to normal conditions.E7 regulated the mRNA level of all the genes studied, in all conditions, suggesting that the Rb family or other E7-interacting proteins might modify the expression of these genes. SIPS modified strongly the E7-mediated regulatory control on p107, p16(Ink-4a), p19(Ink-4d), p27(Kip-1), p21(Waf-1) and Rb mRNA level, when compared to normal conditions. Further work is ongoing to test whether this E7-mediated regulatory control takes place through interactions with Rb or other E7-interacting proteins.

Cell Cycle↗
PubMedDate not supplied

Neurosteroids, brain damage, and mental illness.

The steroidal environment of the brain has marked consequences for both its structure and function. Social or physical stress has deleterious results on hippocampal function. This can be replicated by raising corticoids, which are also highly responsive to stress. Corticosterone, the major glucocorticoid in the rat, induces neuronal death in primary hippocampal cultures. Elevated corticoids also induce mood changes, and these are well known to be associated with stress, particularly chronic stress such as social adversity accentuated by intercurrent aversive life events. DHEA, a second adrenal steroid, has a very different developmental history, increasing rapidly during childhood, reaching a peak in youth, and declining thereafter in both blood and CSF. DHEA, in contrast to corticoids, has brain protective actions. It reduces the neurotoxic actions of glutamate analogues (such as NMDA) as well as those of corticoids. Evidence from several sources suggests that DHEA can act as an antiglucocorticoid. DHEA levels are reduced in major depressive disorders in both adolescents and adults, and a raised cortisol/DHEA ratio (together with intercurrent life events) predicts delayed recovery. DHEA may have a role in the treatment of depression. Together, these findings suggest that altered steroidal environment, whether induced by stress or aging, can have appreciable results on the cellular structure of the brain as well as on its function, although links between the two sets of findings are still tentative.

Adrenal Cortex Hormones↗
PubMed1999

Iron-regulatory proteins, iron-responsive elements and ferritin mRNA translation.

Iron plays a central role in the metabolism of all cells. This is evident by its major contribution to many diverse functions, such as DNA replication, bacterial pathogenicity, photosynthesis, oxidative stress control and cell proliferation. In mammalian systems, control of intracellular iron homeostasis is largely due to posttranscriptional regulation of binding by iron-regulatory RNA-binding proteins (IRPs) to iron-responsive elements (IREs) within ferritin and transferrin receptor (TfR) mRNAs. the TfR transports iron into cells and the iron is subsequently stored within ferritin. IRP binding is under tight control so that it responds to changes in intracellular iron requirements in a coordinate manner by differentially regulating ferritin mRNA translational efficiency and TfR mRNA stability. Several different stimuli, as well as intracellular iron levels and oxidative stress, are capable of regulating these RNA-protein interactions. In this mini-review, we shall concentrate on the mechanisms underlying modulation of the interaction of IRPs and the ferritin IRE and its role in regulating ferritin gene expression.

Animals↗
PubMed1997

Confirmation of association between attention deficit hyperactivity disorder and a dopamine transporter polymorphism.

Attention deficit hyperactivity disorder (ADHD) is a common condition of childhood the symptoms of which include inattention, excessive motor activity, inpulsivity and distractibility. It is strongly familial and twin and adoption studies suggest that the familiality is due, at least in part, to shared genes. Gillis et al found concordance rates in ADHD for MZ and DZ twins of 81% and 29% respectively. Stimulant drugs (eg, methylphenidate) are effective in the treatment of ADHD and inhibit the dopamine transporter. This has led to the development of a hypodopaminergic hypothesis for the disease. Cook et al examined a 3' variable number of tandem repeat (VNTR) polymorphism at the dopamine transporter gene (DAT1) in a sample of 49 ADHD patients and their parents, using the haplotype relative risk (HRR) method. They found a significant association (chi 2 = 7.29, 1 d.f., P = 0.007) between ADHD and the 480-bp DAT1 VNTR allele. The authors stressed the importance of independent replication and we have achieved this in a study of 40 probands and their parents, using the same robust HRR method. As in the study of Cook et al we found that the 480-bp allele was preferentially transmitted to ADHD probands (chi 2 = 6.07, 1 d.f., P = 0.014).

Alleles↗
PubMed2001

Temporal gene regulation during HIV-1 infection of human CD4+ T cells.

CD4(+) T-cell depletion is a characteristic of human immunodeficiency virus type 1 (HIV-1) infection. In this study, modulation of mRNA expression of 6800 genes was monitored simultaneously at eight time points in a CD4(+) T-cell line (CEM-GFP) during HIV infection. The responses to infection included: (1) >30% decrease at 72 h after infection in overall host-cell production of monitored mRNA synthesis, with the replacement of host-cell mRNA by viral mRNA, (2) suppression of the expression of selected mitochondrial and DNA repair gene transcripts, (3) increased expression of the proapoptotic gene and its gene p53-induced product Bax, and (4) activation of caspases 2, 3, and 9. The intense HIV-1 transcription resulted in the repression of much cellular RNA expression and was associated with the induction of apoptosis of infected cells but not bystander cells. This choreographed host gene response indicated that the subversion of the cell transcriptional machinery for the purpose of HIV-1 replication is akin to genotoxic stress and represents a major factor leading to HIV-induced apoptosis.

CD4-Positive T-Lymphocytes↗
PubMed2004

The detection of non-O157 E. coli in food by immunomagnetic separation.

AIMS: To compare immunomagnetic separation (IMS) protocols (enrichment media and temperature) for the isolation of Escherichia coli serotypes O26 and O111 from four different foods. METHODS AND RESULTS: Foods (minced beef, cheese, apple juice and pepperoni) spiked with low numbers (<100 g(-1)) of stressed nalidixic mutant E. coli serotypes O26 and O111 were enriched in media based on buffered peptone water (BPW), tryptone soya and EC broths incubated at temperatures of 37 and 42 degrees C to optimize the IMS technique. BPW enrichments gave increased recoveries of both serotypes compared with tryptone soya and EC broths. Elevated temperatures of incubation at 42 degrees C were superior to 37 degrees C. CONCLUSIONS: Positive detection of low numbers of stressed target pathogens in all replicate tests was only possible using BPW enrichments. The majority of tests from alternative enrichments resulted in zero or single colonies recovered post-IMS. SIGNIFICANCE AND IMPACT OF THE STUDY: The optimum IMS protocol would improve isolation rates of E. coli O26 and O111 from foods and lead to increased safety for the consumer. Sub-optimal IMS protocols could lead to foods being incorrectly labelled free from these pathogens.

Beverages↗
PubMed2006

Deregulation of DNA damage signal transduction by herpesvirus latency-associated M2.

Infected cells recognize viral replication as a DNA damage stress and elicit a DNA damage response that ultimately induces apoptosis as part of host immune surveillance. Here, we demonstrate a novel mechanism where the murine gamma herpesvirus 68 (gammaHV68) latency-associated, anti-interferon M2 protein inhibits DNA damage-induced apoptosis by interacting with the DDB1/COP9/cullin repair complex and the ATM DNA damage signal transducer. M2 expression constitutively induced DDB1 nuclear localization and ATM kinase activation in the absence of DNA damage. Activated ATM subsequently induced Chk activation and p53 phosphorylation and stabilization without eliciting H2AX phosphorylation and MRN recruitment to foci upon DNA damage. Consequently, M2 expression inhibited DNA repair, rendered cells resistant to DNA damage-induced apoptosis, and induced a G(1) cell cycle arrest. Our results suggest that gammaHV68 M2 blocks apoptosis-mediated intracellular innate immunity, which might ultimately contribute to its role in latent infection.

Active Transport, Cell Nucleus↗
PubMed2003

Double-stranded RNA activates a p38 MAPK-dependent cell survival program in biliary epithelia.

Double-stranded RNA (dsRNA) is produced during replicative viral infection or genotoxic stress. Thus knowledge of the cellular response to dsRNA is necessary to understand the effects of DNA damage or viral infection in biliary epithelia. We assessed the effect of dsRNA on biliary epithelial cell proliferation and apoptosis and the role of the stress-activated p38 MAPK signaling pathway in these responses. dsRNA did not induce apoptosis or proliferation in Mz-ChA-1 human malignant cholangiocytes, but decreased cytotoxicity induced by camptothecin or tumor necrosis factor-related apoptosis inducing ligand and decreased activity of caspases 3, 8, and 9. Furthermore, dsRNA increased p38 MAPK and JNK kinase active site phosphorylation but had no effect on either MAPK kinase (MEK)1/2 or protein kinase R phosphorylation. Inhibition of p38 MAPK with SB-203580 increased basal caspase activity. Thus dsRNA stimulates a p38 MAPK-dependent cell-survival pathway in biliary epithelial cells that may modulate the response of the biliary epithelia to dsRNA produced during genotoxic injury or virus infection.

Apoptosis↗
PubMed2006

Characterization and treatment response of anxious children with asthma.

OBJECTIVES: To compare children with Axis I anxiety disorders and asthma with a matched group of anxious children without asthma on questionnaire measures and response to cognitive-behavioural treatment (CBT) for anxiety. METHOD: A sample of 36 children with comorbid anxiety and asthma, aged 8 to 12 years, were matched for age, sex, and specific anxiety disorder with 36 children with an Axis I anxiety disorder but no asthma. Parents and children completed standardized questionnaires. RESULTS: Children with comorbid anxiety and asthma had significantly more perinatal complications (P = 0.001), and higher total (P = 0.000) and psychological stressors (P = 0.02), especially parent-child problems (P = 0.01), but lower levels of depression (P = 0.03) and anxiety (P = 0.05), compared with anxious, nonasthmatic children. All children reported decreased anxiety (P = 0.001) and depression (P = 0.000) posttreatment, with a trend toward less improvement in anxiety in anxious children with asthma. CONCLUSIONS: Although replication is needed, addressing psychosocial stress and parent-child problems may increase CBT efficacy in children with comorbid anxiety and asthma.

Anxiety Disorders↗
PubMed2006

Advances in macrophage and dendritic cell biology in HIV-1 infection stress key understudied areas in infection, pathogenesis, and analysis of viral reservoirs.

The continued quest to intervene in HIV-1 infection by halting transmission, suppressing replication, or eradicating disease in infected subjects stresses the significance of dendritic cell and macrophage biology as early and persistent players in the relationship between infection and disease. As highlighted by new data and presentations at the Sixth International Workshop on HIV and Cells of Macrophage/Dendritic Lineage and Other Reservoirs, a greater emphasis is currently underway in studying the potential of targeting these cell types by intervention early in infection, better defining viral phenotypes and entry mechanisms with a more precise nomenclature system, identifying new, intrinsic cellular factors that may restrict infection within these cell types, and pursuing novel roles for macrophage activation and trafficking. Other key areas include examination of these cells as sources of viral persistence in patients, their roles in coinfection, and their metabolic function in HIV pathogenesis and drug toxicity. This issue of JLB contains reviews and original research reports from the workshop, which highlight new findings, current research questions, and key areas in need of future investigation as a result of their significance to HIV prevention and pathogenesis.

Dendritic Cells↗
PubMed1998

Isoproterenol-induced creatine kinase leakage in Langendorff-perfused rat heart associated with significant myocardial edema.

Since the mechanism of creatine kinase (CK) leakage induced by beta-adrenoceptor activation remains unclear, we studied the effects of incremental application (10(-9) to 10(-4) M) of isoproterenol (ISP) on the CK efflux from Langendorff-perfused isolated rat hearts under aerobic conditions. Tissue water content was estimated after the perfusion experiment. ISP-induced dose-dependent CK leakage was noted in a sigmoidal fashion, which showed low temperature-dependency (Q10 of 2.41), sensitivity to cepharantine (10(-6) M) and propranolol (10(-7) to 10(-6) M) without any signs of demand ischemia or oxidant stress. CK liberation was not replicated at all by maneuvers activating cAMP-dependent protein kinase (A-kinase). Myocardial edema noted in the control ISP application was ameliorated by exposure to 10(-6) M propranolol or cepharantine (i.e., significant fall in tissue water content; p < 0.05). Histological study revealed nonspecific myocardial fiber swelling and separation without any myocyte necrosis for all the perfusion groups. These results suggest that ISP-induced CK leakage in this model is not mediated by beta-adrenoceptor stimulation, subsequent A-kinase activation or related demand ischemia, but is attributed most to the direct effects of ISP augmenting sarcolemmal CK and water permeability.

Adrenergic beta-Agonists↗
PubMed2000

Administration of ACTH to restrained, pregnant sows alters their pigs' hypothalamic-pituitary-adrenal (HPA) axis.

This study was designed to examine the physiology and behavior of pigs whose dams were snared and then injected with ACTH during gestation. Administration of ACTH to dams during pregnancy has been shown to replicate the effects of prenatal stress in other species. Control sows (n = 8) were given no treatment, whereas the treatment sows (ACTH, n = 8) were immobilized by snaring the snout and then administered an i.v. injection of ACTH (1 IU/kg BW) weekly from 6 to 12 wk of gestation. A pig was killed from each sow at 1, 30, and 60 d of age. The hypothalamus, pituitary gland, adrenal glands, and liver were immediately obtained to determine the amounts of corticotropin-releasing hormone (CRH), beta-endorphin, and mRNA for pro-opiomelanocorticotropin (POMC), the ACTH receptor (ACTH-R), and insulin-like growth factor I (IGF-I). Pituitary corticotrope and somatotrope cell numbers and adrenal cortex-to-medulla area ratios (CORT:MED) were also determined. Pigs' behaviors were recorded at 6 and 8 wk of age. At 75 d of age, a blood sample was taken and a biopsy puncture was created on one pig from each litter, then pigs were stressed by mixing. Blood was sampled every other day for 10 d to determine plasma cortisol concentrations and differential leukocyte counts. Biopsy damage was evaluated for healing. At 1 d of age, control pigs tended to weigh more (P = .09), have a lower expression of ACTH-R mRNA (P = .01) and IGF-I mRNA (P = .01), and a lower CORT:MED (P = .04) than ACTH pigs. At 30 d of age, control pigs had a greater concentration of beta-endorphin (P = .01) and tended to have a lower concentration of CRH (P = .09) and IGF-I mRNA (P = .10) than ACTH pigs. At 60 d of age, control pigs tended to have lighter pituitary glands (P = .08), a lower expression of POMC mRNA (P = .02), and a CORT:MED (P = .003) than ACTH pigs. At 8 wk of age, control pigs performed a higher frequency of belly nosing (P = .07) and oral vice behaviors (P = .01) than ACTH pigs. In response to mixing stress, control pigs had lesser concentrations of plasma cortisol (P = .03) and healed faster (P = .006) than ACTH pigs. Thus, exogenous ACTH and restraint during gestation alters the HPA axis of the sow's offspring, and during stressful situations later in life health, and therefore welfare, may be compromised.

Adrenal Glands↗
PubMed2022

Battle for Metals: Regulatory RNAs at the Front Line.

Metal such as iron, zinc, manganese, and nickel are essential elements for bacteria. These nutrients are required in crucial structural and catalytic roles in biological processes, including precursor biosynthesis, DNA replication, transcription, respiration, and oxidative stress responses. While essential, in excess these nutrients can also be toxic. The immune system leverages both of these facets, to limit bacterial proliferation and combat invaders. Metal binding immune proteins reduce the bioavailability of metals at the infection sites starving intruders, while immune cells intoxicate pathogens by providing metals in excess leading to enzyme mismetallation and/or reactive oxygen species generation. In this dynamic metal environment, maintaining metal homeostasis is a critical process that must be precisely coordinated. To achieve this, bacteria utilize diverse metal uptake and efflux systems controlled by metalloregulatory proteins. Recently, small regulatory RNAs (sRNAs) have been revealed to be critical post-transcriptional regulators, working in conjunction with transcription factors to promote rapid adaptation and to fine-tune bacterial adaptation to metal abundance. In this mini review, we discuss the expanding role for sRNAs in iron homeostasis, but also in orchestrating adaptation to the availability of other metals like manganese and nickel. Furthermore, we describe the sRNA-mediated interdependency between metal homeostasis and oxidative stress responses, and how regulatory networks controlled by sRNAs contribute to survival and virulence.

Bacteria↗
PubMed1988

Temperature and the cell cycle.

During the period between successive divisions, a cell traverses three stages of interphase: G1 (pre-synthetic interphase), S-phase (DNA synthetic interphase) and G2 (post-synthetic interphase). The time taken for all cells in a meristem to divide (the cell doubling time (cdt] decreases in response to an increase in temperature. For example, the cdt in root meristems of Zea mays decreases 21-fold as the temperature is increased from 3 to 25 degrees C. Whether all phases of the cell cycle alter proportionately with temperature has been ascertained by comparing data from the root meristem of five species: Pisum sativum, Helianthus annuus, Tradescantia paludosa, Allium cepa and Triticum aestivum. In three of the five species there is a disproportionate lengthening of the G1 phase at low temperatures. We suggest that arrest in G1 with the associated 2C amount of DNA, confers maximal protection on the genome of a somatic cell to the stress of low temperature. DNA replication has been studied at different temperatures for Helianthus annuus, Secale cereal and Oryza sativa. The rate of DNA replication, per single replication fork, increases when the temperature is raised, while the distance between initiation points (replicon size) remains constant. The temperature at which the cell cycle has a minimum duration is close to 30 degrees C in many species, and it seems that this optimum temperature is always near the upper temperature limit of the cell cycle. The rate of cell division determines the rates of organ and cell growth. Thus, temperature has a major effect on the way in which meristematic cells are deployed in organogenesis. The rate of organogenesis, in turn, determines the response of the plant to the growing season. We predict that species growing in sub-arctic conditions comprise cells with low DNA contents and hence have the potentialities for rapid cell cycles so that maximum advantage can be taken of a short growing season. Data from Triticum aestivum show that at 5 degrees C, nucleoli are large compared with those at 10-25 degrees C. These observations are consistent with high levels of RNA polymerase and cellular RNA found at low compared with high temperatures. These responses may be important in sustaining growth at 5 degrees C. Finally, the effects of temperature on developmental transitions are discussed. The picture that emerges is that more is known about low, as opposed to high, temperature as a morphogenetic switch but virtually nothing is known about cell cycle activity during such transitions.(ABSTRACT TRUNCATED AT 400 WORDS)

Adaptation, Physiological↗
PubMed1998

[DNA replication: mechanism and significance for general practice].

The maintenance of genetic information in a cell is ensured by essential macromolecular events called DNA replication and DNA repair. The cell possesses many control mechanisms that allow the optimal strategy under extreme physiological conditions. A cell that is in the process of replicating its DNA and faces a genotoxic stress such as UV-damage, X-ray damage and influences of mutagens will turn off DNA replication and instead turn on DNA repair mechanisms. We have learned in the last three years that in all these processes identical DNA synthetic enzymes are involved. They are, however, coordinated to the actually required metabolic events through a ring-shaped protein called proliferating cell nuclear antigen (PCNA). Exact knowledge of these protein-protein interactions will eventually open up novel therapeutic strategies against cancer.

Cell Transformation, Neoplastic↗
PubMed2003

Stress-induced changes in pathophysiology and interferon gene expression during primary HSV-1 infection.

Herpes simplex viruses (HSV) are the cause of the most common clinically recognized herpesvirus infections. The severity and duration of the primary HSV infection have been correlated with the frequency and severity of subsequent recurrences. Reactivation of latent HSV-1 can occur as a result of physical or emotional stress; however, the effects of stress on the modulation of the clinical pathophysiology of primary HSV-1 infections are not well understood. Although it is known that stress can be immunosuppresive, the immunological mechanisms by which stress modulates early immune responses, such as type I interferon gene expression during a primary HSV-1 infection are still not understood. It was hypothesized that due to suppressed early immune responses, stress would increase the severity of a cutaneous primary HSV-1 infection. In this investigation, a cutaneous HSV-1 model in the SKH-1 mouse was characterized and utilized to study the effect of restraint stress on the modulation of the clinical pathophysiology of primary HSV-1. Despite prolonged viral replication at the site of primary infection, restraint stress decreased the clinical severity of primary HSV-1 in the skin of SKH-1 mice. A decrease in type I and type II IFN expression was found in the skin of acutely infected restrained mice when compared to controls at day 3 post-infection using competitive RT-PCR. Using the glucocorticoid-receptor antagonist RU486, IFN-beta and INF-gamma expression were restored in restrained animals to control levels. Treatment with RU486 also increased the clinical severity of the cutaneous infection to control levels in restrained mice. Thus, RST masked the severity of an HSV-1 infection by decreasing its clinical signs while impairing the ability of the host to control viral replication prolonging the infectious period.

Animals↗
PubMed2002

Oxidative stress shortens telomeres.

Telomeres in most human cells shorten with each round of DNA replication, because they lack the enzyme telomerase. This is not, however, the only determinant of the rate of loss of telomeric DNA. Oxidative damage is repaired less well in telomeric DNA than elsewhere in the chromosome, and oxidative stress accelerates telomere loss, whereas antioxidants decelerate it. I suggest here that oxidative stress is an important modulator of telomere loss and that telomere-driven replicative senescence is primarily a stress response. This might have evolved to block the growth of cells that have been exposed to a high risk of mutation.

Cell Division↗