Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0392674 (exhaustion)
 13,658 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

We have analysed the interplay of glucocorticoid receptor (GR) and the lymphocyte-specific factor Oct-2A with transient co-transfection assays. Our data confirm our previously described observation that GR and the apparently unrelated factors belonging to the Octamer family can synergize when permitted to bind in cis. However, when GR binding sites are not present in the reporter genes, we observe that the action of the cloned factor Oct-2A expressed in HeLa cells is strongly inhibited in the presence of active GR molecules. We can demonstrate that this GR-mediated inhibition of Oct-2A action is neither due to competitive binding to DNA target sites nor to a reduction of DNA binding competent Oct-2A in the transfected cells. We observe that the phenomenon is not reciprocal, since co-expression of Oct-2A does not inhibit GR-dependent transcription activation. Furthermore, we provide evidence that the observed GR-Oct-2A interference may be dependent on the type of cell line hosting the co-transfected molecules. We consider it likely that the GR-mediated inhibition is due to the exhaustion of some rate-limiting co-activators.
 ...
PMID:Interference and synergism of glucocorticoid receptor and octamer factors. 171 79

The effect of ATP and factors known to alter cellular ATP level on the properties of cytosolic glucocorticoid receptor of the heart were investigated. We measured the number of binding sites, binding affinity, receptor transformation and nuclear binding. Experiments performed on the cardiac cytosol of adrenalectomized rats labeled with hormone in vitro showed that both isoprenaline treatment and physical exertion to exhaustion decreased the number of triamcinolone acetonide binding sites, but had no significant effect on the binding affinity. Although ATP had an activating effect on the cytosolic steroid-receptor complexes, the results of phase partitioning and DEAE-cellulose chromatography indicated that neither isoprenaline nor exertion to exhaustion had any apparent effect on the equilibrium between the activated and unactivated forms of complexes. The amount of translocated complexes was dependent on the cytosolic receptor concentration. Experiments performed on the heart cytosol labeled with the hormone in vivo, showed that exertion to exhaustion changed the equilibrium between activated and unactivated complexes in favour of the latter form and at the same time decreased the amount of complexes bound to the nuclei and chromatin. It is not clear whether these changes reflect alterations in receptor activation and its accumulation in the nuclei, or whether they are connected with the release of the nuclear receptor due to the decrease in receptor affinity to chromatin or some other nuclear component. Speculatively, the data suggest that glucocorticoid action in heart cells may depend on the ability of cells to maintain a certain level of ATP.
 ...
PMID:The effect of isoprenaline and physical exertion to exhaustion on the mechanism of glucocorticoid action in the rat heart. 373 38

A model of the immobilization stress aided to study the main characteristics of dexametasone-binding and transcortin-like receptors in the liver and heart cytosol, the level of endogenous corticosterone, induction of the glucocorticoid--dependent liver enzyme tyrosine aminotransferase (TATF), and amount of a number of metabolites. The study revealed disturbances of the receptor binding and cellular metabolism during the stress. A sharp increase of endogenous glucocorticoids in blood and tissues along with inhibition of the glucocorticoid receptor binding in organs and of the TATF activity, exhaustion of cellular contents of glucose and cholesterine, a decrease in the protein amount, increasing level of urine in blood and tissues as well as a considerable hyposodiumemia indicate transition of the stress from the compensated phase into the decompensated one.
 ...
PMID:[Glucocorticoid receptors and metabolic disorders of the liver and heart following immobilization]. 611 30

Thymic involution occurs in young adult male Wistar rats that have performed two runs to exhaustion (RTE) on a treadmill, separated by a 24-h rest period, but not after a single RTE. We were interested in determining whether programmed cell death (or apoptosis) is responsible for the corresponding decrease in T-cell numbers in the thymus. DNA fragmentation, which is an early feature of apoptosis and easily detected by agarose gel electrophoresis, was found in rat thymocytes after the second RTE (the duration of 1 RTE was approximately 5 h). It was also detected after a single RTE or after 2.5 h of running only, and the levels of DNA fragmentation were always roughly similar. In addition, DNA fragmentation was decreased in RU-486 vs. vehicle-treated rats that had run for 2.5 h. These results indicate that physical stress induces glucocorticoid receptor-mediated apoptosis of rat thymocytes. Because apoptosis is induced to similar levels during mild and severe physical stresses, some additional events must be associated to provoke thymic involution.
 ...
PMID:Physiological programmed cell death in thymocytes is induced by physical stress (exercise). 821 18

Stressful exercise has been found to reduce the proinflammatory cytokine response to lipopolysaccharide (LPS). In this study, we aimed to determine whether receptor antagonists for corticosterone or catecholamines would increase the LPS-induced tumor necrosis factor-alpha (TNF-alpha) response after exhaustive exercise. Female F344 rats were randomly assigned to one of five groups: control (vehicle), RU-486 (glucocorticoid receptor antagonist, 30 mg/kg)-, propranolol [nonselective beta-adrenergic receptor (AR) blockade, 30 mg/kg]-, atenolol (beta(1)-AR blockade, 30 mg/kg)-, or ICI 118551 (beta(2)-AR blockade, 30 mg/kg)-treated groups. Each antagonist was given intraperitoneally 30 min prior to exercise or control period. Exercised rats ran until exhaustion on a treadmill at gradually increasing speeds, from 10 to 36 m/min at 15% grade. Immediately postexercise or control period all rats were injected with LPS (1 mg/kg, i.v.). Plasma TNF-alpha was reduced by prior exercise to approximately 10% of that of sedentary controls (p < 0.01). Plasma TNF-alpha concentration in exercised RU-486-treated rats was significantly different than that of nonexercised rats (19.2%, p < 0.01) and not different from exercised rats. However, pretreatment of rats with the nonselective beta-AR blocker propranolol almost completely reversed the exercise-induced suppression of plasma TNF-alpha in response to LPS. beta(1)-AR pretreatment almost completely attenuated the exercise-induced suppression of LPS-induced plasma TNF-alpha while beta(2)-antagonism had a partial effect. These results indicate that exercise-induced catecholamines, acting through beta-ARs (especially the beta(1)-AR), are responsible for the exercise-induced suppression of plasma TNF-alpha after LPS administration.
 ...
PMID:Beta-adrenergic receptor blockade attenuates the exercise-induced suppression of TNF-alpha in response to lipopolysaccharide in rats. 1771 56

Stress is a state of derailed homeostasis and a main environmental risk factor for psychiatric diseases. Chronic or uncontrollable stress may lead to a dysregulation of the hypothalamic-pituitary-adrenal (HPA) axis, which is a common feature of stress-related psychiatric disorders. One of the key mechanisms underlying a disturbed HPA axis is an impaired function of the glucocorticoid receptor (GR) with an enhanced or reduced feedback sensitivity for glucocorticoids and subsequently altered concentrations of peripheral cortisol. GR function is regulated by a multiprotein complex including the different expression of the hsp90 co-chaperone FK 506 binding protein 51 (FKBP5) that may be genetically determined or acquired in response to stressful stimuli. Specific patterns of a dysregulation of the HPA axis and GR function are found in different stress-related psychiatric entities e.g. major depression, job-related exhaustion or posttraumatic stress disorder. GR challenge tests like the dexamethasone-suppression test (DST), the dexamethasone-corticotropin-releasing hormone (dex-CRH) test or most recently the analysis of the dexamethasone-induced gene expression are employed to sensitively measure HPA axis activity in these disorders. They provide information for a stratification of phenotypic similar but neurobiological diverse psychiatric disorders. In this review we present a synopsis of GR challenge tests with a focus on the application of the DST, the CRH test and the dex-CRH test as well as the dexamethasone-induced gene expression in stress-related psychiatric entities.
 ...
PMID:How to measure glucocorticoid receptor's sensitivity in patients with stress-related psychiatric disorders. 2944 45