Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0043167 (pertussis)
 19,595 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The EGR-1 gene is an immediate early response gene encoding a zinc finger DNA-binding protein. The present studies have examined the regulation of EGR-1 gene expression in human U-937 monocytic leukemia cells treated with granulocyte-macrophage colony-stimulating factor (GM-CSF). The results demonstrate that GM-CSF rapidly and transiently increases EGR-1 gene expression in U-937 cells. Similar findings were obtained in GM-CSF-treated human monocytes. We also show that the regulation of EGR-1 expression by GM-CSF is a pertussis toxin-sensitive event. The results of nuclear run-on assays further demonstrate that the EGR-1 gene is constitutively transcribed in untreated U-937 cells and that GM-CSF has little effect on this rate of transcription. Inhibition of protein synthesis with cycloheximide also had no detectable effect on EGR-1 gene transcription but was associated with superinduction of EGR-1 mRNA levels in GM-CSF-treated cells. Moreover, the half-life of GM-CSF-induced EGR-1 transcripts was prolonged from 33 to 70 min following inhibition of protein synthesis. Taken together, the results indicate that GM-CSF activates signaling pathways which regulate EGR-1 gene expression through a pertussis toxin-sensitive G protein and that these events increase EGR-1 mRNA levels by a posttranscriptional mechanism. This GM-CSF-dependent regulation of EGR-1 expression may provide a mechanism for transducing signals to the nucleus that are involved in the control of gene transcription.
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PMID:Posttranscriptional regulation of the zinc finger-encoding EGR-1 gene by granulocyte-macrophage colony-stimulating factor in human U-937 monocytic leukemia cells: involvement of a pertussis toxin-sensitive G protein. 206 96

The recent isolation and cloning of the G protein-coupled central cannabinoid receptor (CB1) from brain tissue has provided a molecular basis to elucidate how cannabinoid compounds may mediate their psychoactive effects. Here we report the high expression of cannabinoid receptors in human astrocytoma tumors of different grades, in the astrocytoma cell lines U373 MG and GL-15, as well as in normal astrocytes. From an analysis of the coupling mechanisms of functional CB1 receptors in U373 MG, we show that, in addition to the inhibition of adenylyl cyclase, activation by the cannabinoid agonist CP-55940 induces the expression of the immediate-early gene krox-24, also known as NGFI-A, zif/268, egr-1, and TIS8. The amount of Krox-24 protein and the level of Krox-24 DNA binding activity, as measured by Western blot and electrophoretic mobility shift assay, respectively, were also increased by the addition of CP-55940. These effects were blocked by incubation with pertussis toxin but not by treatment with hydrolysis-resistant cAMP analogues, suggesting that the transduction pathway between the cannabinoid receptor and krox-24 involves a pertussis toxin-sensitive GTP-binding protein and is independent of cAMP metabolism. The specific involvement of CB1 in Krox-24 induction was demonstrated in Chinese hamster ovary cells transfected with the human CB1 receptor and also in experiments using the CB1-selective cannabinoid antagonist SR 141716A.
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PMID:Stimulation of cannabinoid receptor CB1 induces krox-24 expression in human astrocytoma cells. 777 59

Cannabinoids, known for their psychoactive effects, also possess immunomodulatory properties. The recent isolation and cloning of the G-protein-coupled peripheral cannabinoid receptor (CB2), mainly expressed in immune tissues, have provided molecular tools to determine how cannabinoid compounds may mediate immunomodulation. We here investigated the CB2 signaling properties using stably transfected Chinese hamster ovary cells expressing human CB2. First, we showed that stimulation by a cannabinoid agonist activated mitogen-activated protein (MAP) kinase in time- and dose-dependent manners. The rank order of potency for MAP kinase activation of cannabinoid agonists correlated well with their binding capacities. Second, we demonstrated that, following MAP kinase activation, cannabinoids induced the expression of the growth-related gene Krox-24, also known as NGFI-A, zif/268, and egr-1. Pertussis toxin completely prevented both MAP kinase activation and Krox-24 induction, even more these responses appeared to be dependent of specific protein kinase C isoforms and independent of inhibition of adenylyl cyclase. A similar coupling of CB2 to a mitogenic pathway and to the regulation of Krox-24 expression was also observed in human promyelocytic cells HL60. Taken together, these findings provide evidence for a functional role of the CB2 receptor in gene induction mediated by the MAP kinase network.
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PMID:Signaling pathway associated with stimulation of CB2 peripheral cannabinoid receptor. Involvement of both mitogen-activated protein kinase and induction of Krox-24 expression. 864 16

The zinc finger transcription factor early growth response-1 (Egr-1, NGFI-A, zif268, Krox 24, TIS8, ZENK) is upregulated immediately in the brain by cortical spreading depression (CSD) and other preconditioning stimuli and thus might participate in regulation of the overall genomic response to preconditioning. In the present study, the induction of expression of Egr-1 and other early growth response family members was characterized in rat primary cortical neuronal cultures. In neuronal cultures in vitro, depolarization or exposure to extracellular glutamate caused a 4-fold increase in egr-1 mRNA while exposure to extracellular ATP caused a 10-fold increase. The presence of mRNA encoding for multiple types of purinergic receptors was confirmed by RT-PCR. A number of nucleotide agonists proved effective in eliciting an increase in egr-1 mRNA. Over a limited range of concentration, the most effective agonists were ATP > ADP > alpha, beta-methylene ATP > UTP > cAMP > UDP > AMP > adenosine. Pertussis toxin, suramin, reactive blue 2, PPADS, DPCPX and inhibitors of Protein Kinase C, Protein Kinase A and PI3 kinase significantly reduced the upregulation of egr-1 by exposure to extracellular ATP. These findings suggest that neuronal metabotropic purinergic receptor activation contributes to the induction of early growth response transcription factors and may provide a target that can be manipulated to increase ischemic tolerance of the brain in vivo.
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PMID:Regulation of expression of early growth response transcription factors in rat primary cortical neurons by extracellular ATP. 1664 94

Histamine (HA) is recognized by its target cells via four G-protein-coupled receptors, referred to as histamine H1-receptor (H1R), H2R, H3R, and H4R. Both H1R and H4R exert pro-inflammatory functions. However, their signal transduction pathways have never been analyzed in a directly comparable manner side by side. Moreover, the analysis of pharmacological properties of the murine orthologs, representing the main targets of pre-clinical research, is very important. Therefore, we engineered recombinant HEK293 cells expressing either mouse (m)H1R or mH4R at similar levels and analyzed HA-induced signalling in these cells. HA induced intracellular calcium mobilization via both mH1R and mH4R, with the mH1R being much more effective. Whereas cAMP accumulation was potentiated via the mH1R, it was reduced via the mH4R. The regulation of both second messengers via the H4R, but not the H1R, was sensitive to pertussis toxin (PTX). The mitogen-activated protein kinases (MAPKs) ERK 1/2 were massively activated downstream of both receptors and demonstrated a functional involvement in HA-induced EGR-1 gene expression. The p38 MAPK was moderately activated via both receptors as well, but was functionally involved in HA-induced EGR-1 gene expression only in H4R-expressing cells. Surprisingly, in this system p38 MAPK activity reduced the HA-induced gene expression. In summary, using this system which allows a direct comparison of mH1R- and mH4R-induced signalling, qualitative and quantitative differences on the levels of second messenger generation and also in terms of p38 MAPK function became evident.
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PMID:Distinct signalling pathways of murine histamine H1- and H4-receptors expressed at comparable levels in HEK293 cells. 2524 76