Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0848237 (acute stress)
 4,619 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

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.
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PMID:Increased neuronal excitability after long-term O(2) deprivation is mediated mainly by sodium channels. 1076 96

The evolutionary precursor to mammalian natural killer cells in teleost fish is called non-specific cytotoxic cells (NCC). NCC collaborate with other non-specific effector mechanisms to provide innate resistance during acute stress responses. The NCC receptor protein (NCCRP-1) contains 238 amino acid residues and is believed to be a type III membrane protein with three distinct functional domains. The antigen-binding domain has been mapped to amino acids nos. 104-119. The intracellular C-terminus contains a high concentration of potential phosphorylation sites (Y, S, T). Indeed, we have shown that activation of NCC by crosslinking of NCCRP-1 leads to receptor tyrosine and serine phosphorylation. The N-terminus of the molecule is also inside the cells and has as well signature amino acids, proline-rich motifs (PRM), that are indicative of functional relevance. The cytokine/hormone receptor-like PRMs are known docking sites for JAK kinases. We have evidence that following activation, NCCRP-1 comes in contact with JAK kinase and as a result of this interaction, STAT 6 is translocated into the nucleus. These results suggest that NCCRP-1 may play a dual role in the activation of NCC: first, as an antigen recognition molecule necessary for target cell lysis, and second, as an initiator of cytokine release from NCC. Both of these processes are required for a competent innate immune response.
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PMID:The non-specific cytotoxic cell receptor (NCCRP-1): molecular organization and signaling properties. 1160 91

Neutral endopeptidase is a membrane bound enzyme with various functions depending on cell type or tissue origin. Normal development and differentiation of immature B lymphocytes depends on expression of CD10/NEP on B cell progenitors and bone marrow stromal cells. Synthetic glucocorticoid dexamethasone (dex), an immunosuppressive and anti-inflammatory drug, was shown to be a potent modulator of CD10/NEP expressed on cells of non-hematopoietic origin. We investigated the effect of dex on expression of differentiation marker CD10/NEP on immature B cells. The drug was applied in concentrations corresponding to the physiological range. CD10/NEP was measured at three levels of expression: mRNA (by means of duplex PCR), membrane protein marker (FACS analysis) and enzyme activity (hydrolysis of a selective chromogenic substrate). Dex down-regulated CD10/NEP expression on immature B cell line NALM-6 in a concentration- and time-dependent fashion. The effect was detected at all three levels. Dex-induced CD10/NEP down-regulation was mediated via glucocorticoid receptors (GR), as it was fully abrogated by a GR antagonist, RU 38486. That occurred at all three levels. The mechanism of dex-induced CD10/NEP down-regulation is not likely to include selection of cells that are CD10low since the effect was partly reversible after the removal of dex. However, dex-induced CD10/NEP down-regulation did include decreased transcription of the CD10 mRNA. Transcriptional inhibitor actinomycin D completely abolished dex-induced CD10/NEP down-regulation. Since differentiation of normal B lymphocytes is associated with down-regulation of CD10/NEP, the data presented suggest that low, physiologically relevant concentrations of glucocorticoids (such as observed in acute stress) may play a regulatory role in normal development and maturation of B lymphocytes.
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PMID:Receptor-mediated down-regulation of neutral endopeptidase (NEP; EC 3.4.24.11; CD10) on immature B lymphocytes by dexamethasone. 1587 Sep 9

ATP-sensitive potassium (K(ATP)) channels are evolutionarily conserved plasma-membrane protein complexes, widely represented in tissue beds with high metabolic activity. There, they are formed through physical association of the inwardly rectifying potassium channel pore, most typically Kir6.2, and the regulatory sulfonylurea receptor subunit, an ATP-binding cassette protein. Energetic signals, received via tight integration with cellular metabolic pathways, are processed by the sulfonylurea receptor subunit that in turn gates the nucleotide sensitivity of the channel pore thereby controlling membrane potential dependent cellular functions. Recent findings, elicited from genetic disruption of channel proteins, have established in vivo the requirement of intact K(ATP) channels in the proper function of cardiac muscle under stress. In the heart, where K(ATP) channels were originally discovered, channel ablation compromises cardioprotection under ischemic insult. New data implicate the requirement of intact K(ATP) channels for the cardiac adaptive response to acute stress. K(ATP) channels have been further implicated in the adaptive cardiac response to chronic (patho)physiologic hemodynamic load, with K(ATP) channel deficiency affecting structural remodeling, rendering the heart vulnerable to calcium-dependent maladaptation and predisposing to heart failure. These findings are underscored by the identification in humans that defective K(ATP) channels induced by mutations in ABCC9, the gene encoding the cardiac sulfonylurea receptor subunit, confer susceptibility to dilated cardiomyopathy. Thus, in parallel with the developed understanding of the molecular identity and mode of action of K(ATP) channels since their discovery, there is now an expanded understanding of their critical significance in the cardiac stress response in health and disease.
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PMID:Cardiac KATP channels in health and disease. 1591 Aug 78

The neurohormone arginine vasotocin (AVT) in non mammalian vertebrates is homologous to arginine vasopressin (AVP) in mammals. Its actions are mediated via G protein-coupled receptors that belong to the vasotocin/mesotocin family. Because of the known regulatory effects of nonapeptide hormones on anterior pituitary functions, receptor subtypes in that family have been proposed to be located in anterior pituitary cells. Recently, an avian vasotocin receptor subtype designated VT4R has been cloned, which shares 69% sequence homology with a human vasopressin receptor, the V1aR. In the present study, a polyclonal antibody to the VT4R was developed and validated to confirm its specificity to the VT4R. The antibody was used to test the hypothesis that the VT4R is present in the avian anterior pituitary and is specifically associated with certain cell types, where its expression is modulated by acute stress. Western blotting of membrane protein extracts from pituitary tissue, the use of HeLa cells transfected with the VT4R and peptide competition assays all confirmed the specificity of the antibody to the VT4R. Dual-labelling immunofluorescence microscopy was utilised to identify pituitary cell types that contained immunoreactive VT4R. The receptor was found to be widely distributed throughout the cephalic lobe but not in the caudal lobe of the anterior pituitary. Immunoreactive VT4R was associated with corticotrophs. Approximately 89% of immunolabelled corticotrophs were shown to contain the VT4R. The immunoreactive VT4R was not found in gonadotrophs, somatotrophs or lactotrophs. To determine a possible functional role of the VT4R and previously characterised VT2R, gene expression levels in the anterior pituitary were determined after acute immobilisation stress by quantitative reverse transcriptase-polymerase chain reaction. The results showed a significant increase in plasma corticosterone levels (three- to four-fold), a significant reduction of VT4R mRNA and an increase of VT2R mRNA (P < 0.05) in acutely immobilised chicks compared to controls. The data suggest a role of the VT4R in the avian stress response.
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PMID:Distribution of the Vasotocin Subtype Four Receptor (VT4R) in the Anterior Pituitary Gland of the Chicken, Gallus gallus, and its Possible Role in the Avian Stress Response. 2284 30