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Query: UNIPROT:P06889 (Mol)
 630,302 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Hormonal and neurotransmitter environment of nondifferentiated cells in the developing brain determines many of gender-specific behavioural and neuroendocrine functions. Early postnatal and long-term effects of maternal stress or prenatal glucocorticoid on sex-related peculiarities of the brain morphology, biogenic monoamine turnover, testosterone metabolism, hypothalamic noradrenaline (NA) and adrenocortical responses to an acute stress were studied in Wistar rat offsprings. Maternal stress (1 h immobilization daily for gestational days 15-21) prevented development of sexual dimorphism in neuronal cell nuclei volumes in suprachiazmatic nucleus (SCN) in 10 day old pups. That was associated with a disappearance of male female differences in NA and 5-hydroxytryptamine turnover in the preoptic area (POA) and dopamine (DA) turnover in the mediobasal hypothalamus (MBH) by decreasing them in male pups. Hydrocortisone acetate (5 mg daily during the last week of pregnancy) produced changes in NA turnover in the POA of males and females which were quite similar to those after maternal stress. Changes in aromatase and 5alpha-reductase activities in the POA of male pups were quite opposite as affected by maternal stress or prenatal glucocorticoid. Sexual differences in 5alpha-reductase activity in the MBH appeared due to its increase in prenatally stressed male pups. In contrast to adult males, in adult females maternal stress did not restrict hypothalamic NA and blood plasma corticosterone response to acute stress (1 h immobilization). Our findings on morphology and functions of gender-related developing brain areas stand in correlation with modifying effects of maternal stress and prenatal glucocorticoid on behavior and neuroendocrine regulations.
J Steroid Biochem Mol Biol
PMID:Prenatal stress and glucocorticoid effects on the developing gender-related brain. 1041 84

Reactive oxygen species (ROS) are implicated in the pathogenesis of stress-induced gastrointestinal mucosal injury. In the present study, we have investigated the effects of acute and chronic stress on the enhanced production of ROS including superoxide anion [SA; as determined by cytochrome c reduction (CCR)] and hydroxyl radicals (OH), and correlated the enhanced production of these free radicals with increased lipid peroxidation, membrane microviscosity and DNA fragmentation, indices of oxidative tissue damage, in the gastric and intestinal mucosa of female Sprague-Dawley rats. Furthermore, the protective ability of bismuth subsalicylate (BSS) against the gastrointestinal mucosal injury induced by acute and chronic stress was determined. Acute stress was induced for a period of 90 min, while chronic stress was induced for 15 min/day for 15 consecutive days. Half of the animals exposed to acute stress were pretreated orally with 15 mg BSS/kg 30 min prior to the exposure to acute stress. Similarly, half of the animals exposed to water-immersion restraint chronic stress were pretreated orally with 7.5 mg BSS/kg/day for 15 consecutive days 30 min prior to the exposure to chronic stress. Acute stress produced greater injury to both gastric and intestinal mucosa as compared to chronic stress. Acute stress increased CCR and OH production by 10.0- and 14.3-fold, respectively, in the gastric mucosa, and 10.4- and 17.0-fold, respectively, in the intestinal mucosa. Pretreatment with BSS prevented the acute stress-induced increase in CCR and OH production. Acute stress increased lipid peroxidation, DNA fragmentation and membrane microviscosity by 3.6-, 4.0- and 11.6-fold, respectively, in gastric mucosa, and 4.1-, 5.0- and 16.2-fold, respectively, in intestinal mucosa. BSS decreased acute stress-induced lipid peroxidation, DNA fragmentation and membrane microviscosity by approximately 26, 35 and 30%, respectively, in gastric mucosa, and by 20, 36 and 30%, respectively, in the intestinal mucosa. Chronic stress increased CCR and OH production by 4.8- and 6.3-fold, respectively, in gastric mucosa, and 4.6- and 6.9-fold, respectively, in intestinal mucosa. Chronic stress increased lipid peroxidation and DNA fragmentation by 2.9- and 3.3-fold, respectively, in gastric mucosa, and 3.3- and 4.2-fold, respectively, in intestinal mucosa. BSS decreased chronic stress-induced lipid peroxidation, DNA fragmentation and membrane microviscosity by approximately 41, 44 and 45%, respectively, in gastric mucosa, and by 39, 52 and 51%, respectively, in the intestinal mucosa. Daily administration of BSS provided greater protection against chronic stress-induced oxidative gastrointestinal injury as compared to the acute stress. These results demonstrate that both acute and chronic stress can induce gastrointestinal mucosal injury through enhanced production of ROS, and that BSS can significantly protect against gastrointestinal mucosal injury.
Mol Cell Biochem 1999 Jun
PMID:Acute and chronic stress-induced oxidative gastrointestinal mucosal injury in rats and protection by bismuth subsalicylate. 1044 9

The cAMP signalling pathway plays a key role in the regulation of the hypothalamic-pituitary-adrenal axis. Transcription factor CREM (cAMP response element modulator) is implicated in the modulation of a number of neuroendocrine functions. By virtue of an alternative, intronic promoter CREM generates the powerful transcriptional repressor ICER (inducible cAMP early repressor), which displays a pronounced neuroendocrine-specific expression. Here we document a remarkable induction of ICER in response to acute stress in the intermediate lobe (IL) of the pituitary gland. The induction is transient and is preceded by CREB phosphorylation. Adrenergic stimulation directs ICER induction in the IL through the activation of both beta2-adrenergic and corticotrophin-releasing hormone receptors. These receptors are positively coupled to the adenylate cyclase signalling pathway, which regulates hormone release from the IL, implicating ICER in the modulation of peptide secretion. We show that targeted ablation of the CREM gene in the mouse causes a chronic increase of beta-endorphin levels. Altered hormonal production occurs both in basal conditions and after stress. Thus, early ICER induction in the IL may be involved in the modulation of gene expression in response to stress.
Mol Cell Endocrinol 1999 Sep 10
PMID:The inducible cyclic adenosine monophosphate early repressor (ICER) in the pituitary intermediate lobe: role in the stress response. 1058 Aug 43

Norepinephrine (NE) is thought to play a role in the stress response, and may be involved in stress-related psychopathological conditions such as depression or anxiety. Heterogeneity in individual responses to the same stressor suggest that a genetic susceptibility to the effects of stress may contribute to such pathology. To address possible mechanisms underlying this genetic aspect of the stress response, we examined acute stress-induced changes in mRNA expression for several components of the NE system in the locus coeruleus (LC) and adrenal medullae of stress-susceptible Wistar-Kyoto (WKY) rats and their parent Wistar (W) strain. Expression of tyrosine hydroxylase (TH), NE transporter (NET) and alpha(2A) receptor mRNA were measured in the LC by in situ hybridization 30 min and 2 h after the onset of 30 min restraint stress. Adrenal TH mRNA was measured by slot blots. No basal differences were observed for any measure, but in the LC, expression of TH mRNA increased by 40% in W rats at 30 min (n=8, p<0.05) and returned toward baseline by 2 h, while WKY rats showed only a non-significant 29% increase at 2 h. In contrast, adrenal TH mRNA expression increased in WKY rats at 2 h (n=3, p<0.05), with no significant change in W rats. NET and alpha(2A) mRNA were unaltered by restraint stress in both strains. Differences in the stress-reactivity of TH gene expression in the central and peripheral noradrenergic systems may be related to differences in behavioral coping strategies and autonomic responsivity to stress in these strains, and suggest that differences in noradrenergic reactivity may contribute to genetic susceptibility to stress-related pathology.
Brain Res Mol Brain Res 2000 Jan 10
PMID:Effects of acute restraint stress on tyrosine hydroxylase mRNA expression in locus coeruleus of Wistar and Wistar-Kyoto rats. 1064 82

Sympathetic activation leading to increased levels of blood catecholamines, and stimulation of the hypothalamic-pituitary inter-renal axis leading to increased cortisol, are difficult to avoid when handling animals. Yet, in research on effects of acute stress, elicitation of such responses must be minimized in the control groups. The work examines means to achieve a minimally disturbed state in rainbow trout (Oncorhynchus mykiss). Level of arousal was determined by adrenaline and cortisol concentrations in plasma, and by the spleen:somatic index. Fish were prepared for bleeding by rapid capture and concussion, by infusion of anesthetic into the undisturbed home tank, by confinement in black boxes, or by being fed alpha- and beta-receptor antagonists. Even when done quickly, netting and concussion yielded fish with ca. 200-pmol adrenaline/ml plasma. Cortisol was elevated (to > 10 ng/ml) within 30 s of stress initiation. Surreptitious infusion of anesthetic (2-phenoxyethanol, PE) into tanks yielded fish with lower adrenaline levels (means 19.34 and 19.58 pmols/ml in home tank and black boxes, respectively). Among fish given phentolamine and propranolol, spleen:somatic indices and plasma adrenaline were higher than in diet controls, whether undisturbed or stressed, indicative of successful receptor blockade. Since careful infusion of 2-PE yielded the lowest adrenaline levels, and requires no special apparatus, it is the method of choice for obtaining minimally stressed fish.
Comp Biochem Physiol A Mol Integr Physiol 1999 Nov
PMID:Modulation of stress hormones in rainbow trout by means of anesthesia, sensory deprivation and receptor blockade. 1066 82

We have previously observed that prolonged O(2) deprivation alters membrane protein expression and membrane properties in the central nervous system. In this work, we studied the effect of prolonged O(2) deprivation on the electrical activity of rat cortical and hippocampal neurons during postnatal development and its relationship to Na(+) channels. Rats were raised in low O(2) environment (inspired O(2) concentration = 9.5+/-0.5%) for 3-4 weeks, starting at an early age (2-3 days old). Using electrophysiologic recordings in brain slices, RNA analysis (northern and slot blots) and saxitoxin (a specific ligand for Na(+) channels) binding autoradiography, we addressed two questions: (1) does long-term O(2) deprivation alter neuronal excitability in the neocortical and hippocampal neurons during postnatal development? and (2) if so, what are the main mechanisms responsible for the change in excitability in the exposed brain? Our results show that (i) baseline membrane properties of cortical and hippocampal CA1 neurons from rats chronically exposed to hypoxia were not substantially different from those of naive neurons; (ii) acute stress (e.g., hypoxia) elicited a markedly exaggerated response in the exposed neurons as compared to naive ones; (iii) chronic hypoxia tended to increase Na(+) channel mRNA and saxitoxin binding density in the cortex and hippocampus as compared to control ones; and (iv) the enhanced neuronal response to acute hypoxia in the exposed cortical and CA1 neurons was considerably attenuated by applying tetrodotoxin, a voltage-sensitive Na(+) channel blocker, in a dose-dependent manner. We conclude that prolonged O(2) deprivation can lead to major electrophysiological disturbances, especially when exposed neurons are stressed acutely, which renders the chronically exposed neurons more vulnerable to subsequent micro-environmental stress. We suggest that this Na(+) channel-related over-excitability is likely to constitute a molecular mechanism for some neurological sequelae, such as epilepsy, resulting from perinatal hypoxic encephalopathy.
Brain Res Mol Brain Res 2000 Mar 29
PMID:Increased neuronal excitability after long-term O(2) deprivation is mediated mainly by sodium channels. 1076 96

Neuronal glucocorticoid receptor (GR) and mineralocorticoid receptor (MR) proteins mediate the transcriptional effects of circulating glucocorticoids. These receptors bind the same DNA response element, yet mediate quite different cellular functions. The present study tests the hypothesis that acute and chronic stress, which cause increases in glucocorticoids sufficient to bind the GR, will regulate expression of the GR and MR genes in the hippocampal formation. Analysis of MR gene transcription using an intronic MR probe revealed a transient 50% decrease in MR hnRNA in CA1, CA3 and dentate gyrus at 60-120 min post-stress, consistent with glucocorticoid down-regulation of the MR gene. However, no changes were seen in full-length MR mRNA at any post-stress time point. In contrast, GR hnRNA was not affected by acute stress, but GR mRNA was decreased 120 min post stress in all hippocampal subregions. Chronic stress exposure down-regulated GR mRNA in CA3 only; effects were first evident 7 days post stress and persisted for the entire stress time-course (28 days). There was no evidence for down-regulation of GR hnRNA or MR hnRNA/mRNA at any point in the chronic stress regimen. The transient decrease in MR hnRNA in the absence of mRNA changes suggests increased MR mRNA stability. In contrast, acute stress decreases the availability of GR mRNA without demonstrably affecting transcription, suggesting reduced GR mRNA stability. The results suggest that acute stress alters GR mRNA expression by largely post-transcriptional mechanisms. However, elevations in basal corticosterone secretion seen following chronic stress are not sufficient to markedly down-regulate GR/MR expression in a long-term fashion.
Brain Res Mol Brain Res 2000 Sep 15
PMID:Stress regulation of adrenocorticosteroid receptor gene transcription and mRNA expression in rat hippocampus: time-course analysis. 1103 47

1. The role of alpha1-adrenergic receptors on CRH mRNA levels in the PVN was studied in control and stressed rats receiving i.c.v. injections of the alpha1-adrenergic agonist, methoxamine, or the alpha1- antagonist, prazosin. 2. Plasma ACTH increased significantly 60 min and 4 hr after a single injection of methoxamine (100 microg, i.c.v.). No desensitization of this response was observed after repeated injections every 6 hr for 24 hr. Concomitantly, POMC mRNA in the anterior pituitary increased by 25% at 4 hr after a single injection and by 96% after repeated injections. 3. CRH mRNA levels in the PVN increased by 131% after repeated injections for 24 hr, but were unchanged 4 hr after a single injection. Central alpha-adrenergic blockade with prazosin did not prevent the increases in CRH mRNA following 4 hr of acute stress, but significantly reduced the increases observed 24 hr after an i.c.v. injection of 75 microg of colchicine or after repeated i.p. hypertonic saline injections every 8 hr. 4. These studies demonstrate that while alpha1-adrenergic receptors contribute to longterm increases of CRH mRNA levels in the PVN during prolonged stress, other factors are likely to be involved in the stimulation of CRH mRNA following acute stimulation.
Cell Mol Neurobiol 2000 Dec
PMID:Role of alpha-1-adrenergic receptors in the regulation of corticotropin-releasing hormone mRNA in the paraventricular nucleus of the hypothalamus during stress. 1110 Sep 76

The anti-inflammatory cytokine IL-10 is up-regulated in response to TNF-alpha suggesting a control mechanism of inflammation. In addition, we recently found systemic IL-10 release in response to acute stress reactions in the absence of any systemic inflammation. In vitro and in vivo studies in experimental models suggest that catecholamines induce IL-10 release via a cyclic adenosine monophosphate/protein kinase A (cAMP/PKA) dependent pathway. Here we studied patients for plasma IL-10 after acute myocardial infarction, a very stressful event without significant signs of systemic inflammation. In fact, the activation of the sympathetic system initiated by cardiac infarction was accompanied by a temporary systemic release of IL-10. Catecholamine induced IL-10 may be released by different cells. Recently, we demonstrated that catecholamines directly stimulate the IL-10 promoter/enhancer via a cAMP/PKA pathway in monocytic cells. A cAMP responsive element (CRE) was identified as major target. Here we show that there is no influence of catecholamines on the IL-10 promoter activity in T-cells. In contrast to monocytic cells, in T-cells cAMP-induced PKA-dependent phosphorylation of the CRE-binding protein 1 (CREB-1) seems to play a marginal role in IL-10 induction, which was reflected by a low cAMP-dependent IL-10-promoter/enhancer stimulation in reporter gene assays. Thus, catecholamines are directly involved in the regulation of IL-10 expression in monocytic but not in T-cells after acute stressful conditions.
Mol Cell Biochem 2000 Sep
PMID:Catecholamines induce IL-10 release in patients suffering from acute myocardial infarction by transactivating its promoter in monocytic but not in T-cells. 1110 35

Previous studies have demonstrated that acute stress leads to the appearance of T-lymphocytes in skin and bone marrow. In order to examine the effects of adrenergic stimulation on the traffic of immune lymphocytes to the lung, C57BL/6 mice were injected with epinephrine subcutaneously, and changes in lymphocyte representation in lung, hilar lymph node, spleen, and blood were examined at 30 min. Cytofluorimetric lymphocyte subset analysis showed that epinephrine increased "memory" CD4+ lymphocytes in enzymatic digests of lung but decreased their representation in spleen. NK1.1+ lymphocytes were concomitantly increased in lung and decreased in spleen. Next, lymphocytes in spleen or popliteal lymph nodes were labeled with the Hoechst lipophilic red dye PKH26 in vivo 48 h prior to epinephrine injection. PKH26+ lymphocytes were identified in lung tissue at 30 min postepinephrine but not in controls. Lymphocyte traffic was inhibited by propanolol. We conclude that epinephrine promotes rapid shifts in immune lymphocytes from lymphoid tissues into lung and blood. Directed traffic of immune lymphocytes may be a feature of the adaptive immune response to stress at mucosal barrier surfaces.
Exp Mol Pathol 2001 Feb
PMID:Epinephrine yields translocation of lymphocytes to the lung. 1117 Jul 85


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