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At least 973 records · Page 54Linked to original sources
PubMed2005

Endogenous coactivator ARA70 interacts with estrogen receptor alpha (ERalpha) and modulates the functional ERalpha/androgen receptor interplay in MCF-7 cells.

Overexpression of androgen receptor (AR) decreases estrogen receptor alpha (ERalpha) transactivation, which plays a basic role in hormone-dependent breast cancer. This transcriptional interference can be due to shared coactivators. Here we demonstrated that in MCF-7 cells ARA70, an AR-specific coactivator, interacted with endogenous ERalpha, increasing its transcriptional activity, and it was recruited to the pS2 gene promoter. Moreover, a dominant negative ARA70 down-regulated ERalpha transcriptional activity as well as pS2 mRNA. ARA70 overexpression reversed the AR down-regulatory effect on ERalpha signaling. However, in the presence of a progressive increase of transfected AR, ARA70 switched into enhancing the inhibitory effect of AR on ERalpha signaling. These opposite effects of ARA70 were further evidenced by coimmunoprecipitation assay in MCF-7wt, MCF-7-overexpressing AR, and HeLa cells, exogenously expressing an excess of ERalpha with respect to AR or an excess of AR with respect to ERalpha. Thus, ARA70 is a coactivator for ERalpha and may represent a functional link between ERalpha/AR modulating their cross-talk in models of estrogen signaling in MCF-7 and HeLa cells.

Blotting, Western↗
PubMed2005

Sertoli-germ cell anchoring junction dynamics in the testis are regulated by an interplay of lipid and protein kinases.

When Sertoli and germ cells were co-cultured in vitro in serum-free chemically defined medium, functional anchoring junctions such as cell-cell intermediate filament-based desmosome-like junctions and cell-cell actin-based adherens junctions (e.g. ectoplasmic specialization (ES)) were formed within 1-2 days. This event was marked by the induction of several protein kinases such as phosphatidylinositol 3-kinase (PI3K), phosphorylated protein kinase B (PKB; also known as Akt), p21-activated kinase-2 (PAK-2), and their downstream effector (ERK) as well as an increase in PKB intrinsic activity. PI3K, phospho (p)-PKB, and PAK were co-localized to the site of apical ES in the seminiferous epithelium of the rat testis in immunohistochemistry studies. Furthermore, PI3K also co-localized with p-PKB to the same site in the epithelium as determined by fluorescence microscopy, consistent with their localization at the ES. These kinases were shown to associate with ES-associated proteins such as beta1-integrin, phosphorylated focal adhesion kinase, and c-Src by co-immunoprecipitation, suggesting that the integrin.laminin protein complex at the apical ES likely utilizes these protein kinases as regulatory proteins to modulate Sertoli-germ cell adherens junction dynamics via the ERK signaling pathway. To validate this hypothesis further, an in vivo model using AF-2364 (1-(2,4-dichlorobenzyl)-1H-indazole-3-carbohydrazide) to perturb Sertoli-germ cell anchoring junction function, inducing germ cell loss from the epithelium in adult rats, was used in conjunction with specific inhibitors. Interestingly, the event of germ cell loss induced by AF-2364 in vivo was also associated with induction of PI3K, p-PKB, PAK-2, and p-ERK as well as a surge in intrinsic PKB activity. Perhaps the most important of all, pretreatment of rats with wortmannin (a PI3K inhibitor) or anti-beta1-integrin antibody via intratesticular injection indeed delayed AF-2364-induced spermatid loss from the epithelium. In summary, these results illustrate that Sertoli-germ cell anchoring junction dynamics in the testis are regulated, at least in part, via the beta1-integrin/PI3K/PKB/ERK signaling pathway.

Androstadienes↗
PubMed2005

Calmodulin and calcium interplay in the modulation of TRPC5 channel activity. Identification of a novel C-terminal domain for calcium/calmodulin-mediated facilitation.

TRPC5 forms Ca2+-permeable nonselective cation channels important for neurite outgrowth and growth cone morphology of hippocampal neurons. Here we studied the activation of mouse TRPC5 expressed in Chinese hamster ovary and human embryonic kidney 293 cells by agonist stimulation of several receptors that couple to the phosphoinositide signaling cascade and the role of calmodulin (CaM) on the activation. We showed that exogenous application of 10 microM CaM through patch pipette accelerated the agonist-induced channel activation by 2.8-fold, with the time constant for half-activation reduced from 4.25 +/- 0.4 to 1.56 +/- 0.85 min. We identified a novel CaM-binding site located at the C terminus of TRPC5, 95 amino acids downstream from the previously determined common CaM/IP3R-binding (CIRB) domain for all TRPC proteins. Deletion of the novel CaM-binding site attenuated the acceleration in channel activation induced by CaM. However, disruption of the CIRB domain from TRPC5 rendered the channel irresponsive to agonist stimulation without affecting the cell surface expression of the channel protein. Furthermore, we showed that high (>5 microM) intracellular free Ca2+ inhibited the current density without affecting the time course of TRPC5 activation by receptor agonists. These results demonstrated that intracellular Ca2+ has dual and opposite effects on the activation of TRPC5. The novel CaM-binding site is important for the Ca2+/CaM-mediated facilitation, whereas the CIRB domain is critical for the overall response of receptor-induced TRPC5 channel activation.

Amino Acid Sequence↗
PubMed2006

Interplay between chromatin and trans-acting factors regulating the Hoxd4 promoter during neural differentiation.

Correct patterning of the antero-posterior axis of the embryonic trunk is dependent on spatiotemporally restricted Hox gene expression. In this study, we identified components of the Hoxd4 P1 promoter directing expression in neurally differentiating retinoic acid-treated P19 cells. We mapped three nucleosomes that are subsequently remodeled into an open chromatin state upon retinoic acid-induced Hoxd4 transcription. These nucleosomes spanned the Hoxd4 transcriptional start site in addition to a GC-rich positive regulatory element located 3' to the initiation site. We further identified two major cis-acting regulatory elements. An autoregulatory element was shown to recruit HOXD4 and its cofactor PBX1 and to positively regulate Hoxd4 expression in differentiating P19 cells. Conversely, the Polycomb group (PcG) protein Ying-Yang 1 (YY1) binds to an internucleosomal linker and represses Hoxd4 transcription before and during transcriptional activation. Sequential chromatin immunoprecipitation studies revealed that the PcG protein MEL18 was co-recruited with YY1 only in undifferentiated P19 cells, suggesting a role for MEL18 in silencing Hoxd4 transcription in undifferentiated P19 cells. This study links for the first time local chromatin remodeling events that take place during transcriptional activation with the dynamics of transcription factor association and DNA accessibility at a Hox regulatory region.

Animals↗
PubMed2006

Interplay between Ku, Artemis, and the DNA-dependent protein kinase catalytic subunit at DNA ends.

Repair of DNA double strand breaks (DSB) by the nonhomologous end-joining pathway in mammals requires at least seven proteins involved in a simplified two-step process: (i) recognition and synapsis of the DNA ends dependent on the DNA-dependent protein kinase (DNA-PK) formed by the Ku70/Ku80 heterodimer and the catalytic subunit DNA-PKcs in association with Artemis; (ii) ligation dependent on the DNA ligase IV.XRCC4.Cernunnos-XLF complex. The Artemis protein exhibits exonuclease and endonuclease activities that are believed to be involved in the processing of a subclass of DSB. Here, we have analyzed the interactions of Artemis and nonhomologous end-joining pathway proteins both in a context of human nuclear cell extracts and in cells. DSB-inducing agents specifically elicit the mobilization of Artemis to damaged chromatin together with DNA-PK and XRCC4/ligase IV proteins. DNA-PKcs is necessary for the loading of Artemis on damaged DNA and is the main kinase that phosphorylates Artemis in cells damaged with highly efficient DSB producers. Under kinase-preventive conditions, both in vitro and in cells, Ku-mediated assembly of DNA-PK on DNA ends is responsible for a dissociation of the DNA-PKcs. Artemis complex. Conversely, DNA-PKcs kinase activity prevents Artemis dissociation from the DNA-PK.DNA complex. Altogether, our data allow us to propose a model in which a DNA-PKcs-mediated phosphorylation is necessary both to activate Artemis endonuclease activity and to maintain its association with the DNA end site. This tight functional coupling between the activation of both DNA-PKcs and Artemis may avoid improper processing of DNA.

Amino Acid Sequence↗
PubMed2006

Regulatory interplay between proton motive force, ADP, phosphate, and subunit epsilon in bacterial ATP synthase.

ATP synthase couples transmembrane proton transport, driven by the proton motive force (pmf), to the synthesis of ATP from ADP and inorganic phosphate (P(i)). In certain bacteria, the reaction is reversed and the enzyme generates pmf, working as a proton-pumping ATPase. The ATPase activity of bacterial enzymes is prone to inhibition by both ADP and the C-terminal domain of subunit epsilon. We studied the effects of ADP, P(i), pmf, and the C-terminal domain of subunit epsilon on the ATPase activity of thermophilic Bacillus PS3 and Escherichia coli ATP synthases. We found that pmf relieved ADP inhibition during steady-state ATP hydrolysis, but only in the presence of P(i). The C-terminal domain of subunit epsilon in the Bacillus PS3 enzyme enhanced ADP inhibition by counteracting the effects of pmf. It appears that these features allow the enzyme to promptly respond to changes in the ATP:ADP ratio and in pmf levels in order to avoid potentially wasteful ATP hydrolysis in vivo.

Adenosine Diphosphate↗
PubMedDate not supplied

Interplay of cigarette smoking and occupational exposure on specific immunoglobulin E antibodies to cobalt.

The results of a cross-sectional survey of an occupational population (n = 706) exposed to hard metal dust revealed distribution of specific immunoglobulin E antibodies against cobalt-conjugated serum albumin (Co-HSA). This population was segregated with respect to smoking and dust-exposure doses. Standard deviations (0.08-0.13) of Co-HSA RAST were sufficiently small (< 7%) to warrant reproducibility. Confirming evidence for 8 workers who had mean + 3 standard deviations of Co-HSA RAST indices and who had been diagnosed with occupational asthma also provided better sensitivity (8/19) and specificity (687/687) of hard metal asthma, rather than metal-induced asthma. Cobalt exposure resulted in significant increases in Co-HSA RAST indices in males, whose mean index was 1.16 +/- 0.13 in nonexposed subjects and 1.37 +/- 0.13 in exposed subjects. There was no difference, however, in the females. This difference between males and females cannot be explained by differences in ages or dust-exposure doses. Furthermore, the specific RAST indices against Co-HSA displayed a strong correlation not only to the intensity of cobalt exposure (r = .488, p < .001), but to log(total exposure doses) (r = .578, p < .001). These results suggest that Co-HSA RAST might be useful as a biological marker for the allergic etiology of hard metal asthma. Nonexposed smokers had similar mean RAST indices: 1.18 +/- 0.12 IU/ml, compared with 1.15 +/- 0.16 IU/ml for nonexposed subjects who had never smoked. There was no correlation between Brinkman indices (i.e., number of cigarettes/d x y) and RAST indices in any of the male groups. Higher, but not significant, mean RAST indices were found for ex-smokers in both the nonexposed (1.18 +/- 0.14) and exposed subjects (1.26 +/- 0.12), compared with subjects who had never smoked. Serum immunoglobulin E levels in the ex-smokers declined with age after they quit smoking, irrespective of exposure status. In contrast, hard metal (cobalt) exposure elevated specific immunoglobulin E. The results of the study suggest that elimination of hard dust exposure is more important than cessation of smoking in the minimization of risk of bronchial asthma. Hard metal exposure may be a preventable risk factor for occupational asthma.

Adult↗
PubMed2003

The interplay of stop signal inhibition and inhibition of return.

Inhibition of return (IOR) refers to slower responding to a stimulus that appears in the same rather than a different location as that of a preceding stimulus. The goal of the present study was to examine the relationship between IOR and stop signal inhibition. Participants were presented with two stimuli (S1 and S2) on each trial. On half of the trials (go trials), participants were required to make a speeded button-press response to report the location of S1; on the other half of trials (stop trials), they were required to cancel the response to S1, as indicated by the appearance of a stop signal at a variable delay (stop signal delay, SSD) after the appearance of S1. Success in cancelling an S1 response varied directly as a function of the SSD: The longer the delay, the more difficult it was for participants to cancel the prepared response. We examined the magnitude of IOR in the S2 reaction times as a function of whether participants made a correct go response to S1, made an erroneous non-cancelled response to S1, or successfully cancelled a response to S1. Our results indicated that the presentation of a stop signal increased the magnitude of IOR, even when the S1 response was not successfully cancelled. However, this was true only when the to-be-cancelled response involved the same effectors as the response used to reveal IOR. These results suggest that there may be a motor component to IOR that is sensitive to the same inhibitory processes that are used to cancel responses in a stop signal paradigm.

Adult↗
PubMedDate not supplied

The interplay of national, state, and local policy in financing care for drug-affected women and children in California.

Recent prevalence studies in California indicate that perinatal alcohol and other drug use remains a serious issue for large numbers of women and their children. In response, national, state and local policymakers have taken steps to address the problem, including increasing funding for treatment services. To gauge the impact of policy attention to this problem, the Center for the Vulnerable Child at Children's Hospital, Oakland, California, surveyed state and local administrators of programs that serve drug-affected women and children in California. Information collected included the scope of program services, indicators of access, and sources of program funding. Surveyed programs were funded through federal, state, county, and foundation sources. Despite new policy and funding initiatives to serve this population, the study found wide gaps between the kinds of services that are believed to be appropriate for drug-affected women and children and the service system that currently exists. Problems in access to care included long waiting times, exclusion of women from programs based on their pregnancy or parenting status, and exclusion of drug-exposed children from programs with medically based eligibility criteria. Program funding sources appeared to impede access, as traditional federal, state, and county funding sources do not support programs that are comprehensive, family-centered, and easily accessible to these women and children. Analysis of the study data suggests that policymakers consider new approaches to promote access to care for these underserved women and children, particularly now as Congress and the states redesign health and social service funding mechanisms and delivery systems.

Adult↗
PubMed1993

Coping with recent life events: the interplay of personal and collective resources.

The importance of personal and collective resources in coping with recent life events was studied among 230 kibbutz members. The sense of coherence, a global life orientation that detects the ability to avoid stressors and to choose appropriate coping strategies and resources, represented personal resources. Collective resources, embedded in the social system to which one belongs, were measured by membership in a religious kibbutz, the kibbutz being viewed as a powerful, collective-coping resource by itself. Physical well-being, psychological distress, and functional limitations were used as outcome measures. Both types of resources have a salutogenic effect, but sense of coherence appears to be a better resource for avoiding the effect of recent life events and for moderating psychological distress and functional limitation after experiencing such events. The two types of resources have no additive effect, nor do they compensate for each other. Only one significant interaction was found, suggesting that the combination of the two resources is useful in avoiding functional limitation. It is also suggested that collective resources have a slight positive effect on personal resources, which, in turn, take over and become most valuable in coping with recent life events. When stress affects social functioning, these same personal resources facilitate the mobilization of whatever collective resources are available.

Adaptation, Psychological↗
PubMed2004

Signalling by the type 1 insulin-like growth factor receptor: interplay with the epidermal growth factor receptor.

The type 1 insulin-like growth factor receptor (IGF-1R) plays an essential role in mammalian growth and development, and has emerged as a candidate therapeutic target in the treatment of cancer. While the pleiotropic cellular responses elicited following tyrosine phosphorylation of the IGF-1R is usually seen to involve the direct recruitment/activation of classical intracellular effector proteins, it is now clear that cross-talk between the IGF-1R and members of distinct receptor families also plays a significant role in effecting intracellular signalling. In recent years, a number of studies have highlighted the interaction(s) between the IGF-1R and the epidermal growth factor receptor (EGFR), another transmembrane tyrosine kinase that is an established cancer target. This review describes the components of the IGF signalling system and gives an overview of the emerging picture of the interrelationship that is now known to exist between the IGF and EGF receptors.

Cell Line, Tumor↗
PubMed1998

The interplay of drinking patterns and other determinants of health.

The health effects of alcohol are determined not only by level of intake but also by patterns of alcohol use and many other health determinants. This study seeks to identify groups of individuals who share various features in terms of drinking styles and other health indicators. Data used are a subset of the 1990 Ontario Health Survey, corresponding to men and women aged 20-64 with complete data in four substantive areas: alcohol use; demographic characteristics; current health status; and various behavioural risk factors for chronic disease. Cluster analysis was used to groups of male and female respondents who were similar in terms of their style of alcohol use, along with other constructs relevant to health risk and health status. For both sexes, clusters were identified which matched expectation in terms of drinking patterns and other relevant variables. For both sexes, clusters were found with generally higher social class indicators, generally positive health behaviours and health status and drinking patterns which did not include drinking to excess. Clusters were also found for which high-volume drinking occasions corresponded with poor health status and high levels of risk factors for chronic disease. Other unanticipated patterns were also identified. This information may assist in identifying confounding effects in epidemiological studies as well as identifying the characteristics of unique sub-populations which are likely to be the focus of primary prevention efforts.

Journal Article↗
PubMed2004

The interplay between c-Myc oncogene expression and circulating vascular endothelial growth factor (sVEGF), its antagonist receptor, soluble Flt-1 in diffuse large B cell lymphoma (DLBCL): relationship to patient outcome.

UNLABELLED: The c-Myc is a ubiquitous and multifunctional oncogene. Recently, data obtained from experimental study suggests the involvement of c-Myc oncogene in angiogenesis. In the present study the interrelation of sVEGF, sFlt-1 concentrations and c-Myc oncoprotein expression at diagnosis were assessed in DLBCL and their impact on the patient outcome. Forty-five DLBCL patients beside 10 normal controls were included. C-Myc oncoprotein was assessed by immunohistochemistry. SVEGF and sFlt-1 were determined by enzyme linked immunosorbent assay. C-Myc over-expression was detected in 66.6% of DLBCL. The DLBCL patient group with positive c-Myc over-expression showed significantly higher sVEGF and significantly decreased sFlt-1 as compared to group with negative c-Myc over-expression (P = 0.000 and P = 0.009 respectively). SVEGF was positively correlated to sLDH and s.beta2 microglobulin (r = 0.6, P = 0.000, r = 0.69, P = 0.000) respectively. On the other hand sFlt-1 was negatively correlated to sLDH and s.beta2 microglobulin (r - 0.25, P > 0.05, r - 0.49, P = 0.001) respectively. The non-living DLBCL group showed significantly higher expression of c-Myc, higher concentration of sVEGF and lower concentration in sFlt-1 level as compared to the living group (P = 0.000 for all). Multivariate analysis revealed that c-Myc over-expression; high sVEGF and normal sFlt-1 levels at diagnosis had independent adverse influence on survival (relative risk: 17.9, 35.7, 29.3, 2.63; P < 0.0001, P < 0.0001, and P = 0.03 respectively) IN CONCLUSION: C-Myc over-expression significantly associated with high sVEGF and normal sFlt-1 level in DLBCL patients, suggesting a complex interrelationship between c-Myc oncogene expression and angiogenic regulators. C-Myc over-expression, high sVEGF and normal sFLt-1 levels at diagnosis had an independent adverse influence on survival in DLBCL patients and considered bad prognostic markers.

Adult↗