Additive Induction of <i>Egr‐1 (zif/268)</i> mRNA Expression in Neuroblastoma × Glioma Hybrid NG108‐15 Cells via Cholinergic Muscarinic, α<sub>2</sub>‐Adrenergic, and Bradykinin Receptors

Katayama, Naoko; Iwata, Emi; Sakurai, Hiroaki; Tsuchiya, Tomofusa; Tsuda, Masashi

doi:10.1111/j.1471-4159.1993.tb03235.x

Cited by 16 publications

(12 citation statements)

References 24 publications

(22 reference statements)

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“…These results confirm and extend the observation that muscarinic AChRs increase Egr-1 message in PC12 (42,57,58), NG108 -15 (59), and 3T3 cells transfected with m1 AChR cells (22). Our data show that in addition to Egr-1, the expression of Egr-2, Egr-3, and Egr-4 is under the control of muscarinic AChRs.…”

Section: Fig 3 Stimulated M1achr Increase Cellular Concentration Ofsupporting

confidence: 90%

Muscarinic Acetylcholine Receptors Activate Expression of the Egr Gene Family of Transcription Factors

Kammer

Mayhaus

Albrecht

et al. 1998

Journal of Biological Chemistry

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In order to search for genes that are activated by muscarinic acetylcholine receptors (mAChRs), we used an mRNA differential display approach in HEK293 cells expressing m1AChR. The zinc-finger transcription factor genes Egr-1, Egr-2, and Egr-3 were identified. Northern blot analyses confirmed that mRNA levels of Egr-1, Egr-2, and Egr-3 increased readily after m1AChR stimulation and that a maximum was attained within 50 min. At that time, Egr-4 mRNA was also detectable. Western blots and electromobility shift assays demonstrated synthesis of EGR-1 and EGR-3, as well as binding to DNA recognition sites in response to m1AChR activation. Activation of m1AChR increased transcription from EGRdependent promoters, including the acetylcholinesterase gene promoter. Activity-dependent regulation of Egr-1 mRNA expression and EGR-1 protein synthesis was also observed in cells expressing m2, m3, or m4AChR subtypes. Increased EGR-1 synthesis was mimicked by phorbol myristate acetate, but not by forskolin, and receptor-stimulated EGR-1 synthesis was partially inhibited by phorbol myristate acetate down-regulation. Together, our results demonstrate that muscarinic receptor signaling activates the EGR transcription factor family and that PKC may be involved in intracellular signaling. The data suggest that transcription of EGRdependent target genes, including the AChE gene, can be under the control of extracellular and intracellular signals coupled to muscarinic receptors. Muscarinic acetylcholine receptors (mAChRs)1 are members of a superfamily of G protein-coupled cell surface receptors with seven transmembrane domain topology. Five subtypes of mAChRs (m1-m5) can be divided according to their signaling mechanisms: m1, m3, and m5 AChRs preferentially couple to the pertussis toxin-insensitive Gq/G11 proteins that stimulate phosphoinositide hydrolysis, whereas m2 and m4 subtypes couple to the G i /G o proteins that predominantly inhibit adenylyl cyclase (1, 2). In brain, mAChRs are involved in such functions as attention, learning, memory, and cognition (3, 4). m1 and m3 AChR subtypes are localized to the somatodendritic cell surfaces of large pyramidal neurons throughout the cortex and the hippocampus, as well as on small cholinergic interneurons in the striatum. In contrast, m2 and m4 AChRs are predominantly present on axons of the large basal forebrain projection neurons that innervate cholinergic target cells throughout the cortex and the hippocampus. Activation of the postsynaptic m1/ m3/m5 AChR family by acetylcholine triggers a large variety of distinct signaling cascades including phospholipase D, adenylyl cyclase, phospholipase A2, the generation of diacylglycerol which activates protein kinase C (PKC) and couples mAChRs to the ERK-MAP-kinase signaling cascade, activation of endoplasmic reticulum IP3 receptors, stimulation of ligand-operated cell-surface Ca 2ϩ channels, and the activity of voltagegated potassium channels (5-12). Cellular responses of mAChRs include the activation of neurite outgrowth, the finetuning of me...

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Section: Fig 3 Stimulated M1achr Increase Cellular Concentration Ofsupporting

confidence: 90%

Muscarinic Acetylcholine Receptors Activate Expression of the Egr Gene Family of Transcription Factors

Kammer

Mayhaus

Albrecht

et al. 1998

Journal of Biological Chemistry

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“…Furthermore, BK induced EGR-1 expression (Fig. 5B+C) in accord with previously observed effects of BK on EGR-1 expression in human fibroblasts or NG108-15 neuroblastoma cells [30], [31]. BK also activated the NFAT reporter (Fig.…”

Section: Resultssupporting

confidence: 90%

Human Mas-Related G Protein-Coupled Receptors-X1 Induce Chemokine Receptor 2 Expression in Rat Dorsal Root Ganglia Neurons and Release of Chemokine Ligand 2 from the Human LAD-2 Mast Cell Line

et al. 2013

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Primate-specific Mas-related G protein-coupled receptors-X1 (MRGPR-X1) are highly enriched in dorsal root ganglia (DRG) neurons and induce acute pain. Herein, we analyzed effects of MRGPR-X1 on serum response factors (SRF) or nuclear factors of activated T cells (NFAT), which control expression of various markers of chronic pain. Using HEK293, DRG neuron-derived F11 cells and cultured rat DRG neurons recombinantly expressing human MRGPR-X1, we found activation of a SRF reporter gene construct and induction of the early growth response protein-1 via extracellular signal-regulated kinases-1/2 known to play a significant role in the development of inflammatory pain. Furthermore, we observed MRGPR-X1-induced up-regulation of the chemokine receptor 2 (CCR2) via NFAT, which is considered as a key event in the onset of neuropathic pain and, so far, has not yet been described for any endogenous neuropeptide. Up-regulation of CCR2 is often associated with increased release of its endogenous agonist chemokine ligand 2 (CCL2). We also found MRGPR-X1-promoted release of CCL2 in a human connective tissue mast cell line endogenously expressing MRGPR-X1. Thus, we provide first evidence to suggest that MRGPR-X1 induce expression of chronic pain markers in DRG neurons and propose a so far unidentified signaling circuit that enhances chemokine signaling by acting on two distinct yet functionally co-operating cell types. Given the important role of chemokine signaling in pain chronification, we propose that interruption of this signaling circuit might be a promising new strategy to alleviate chemokine-promoted pain.

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“…The neurotransmitters directly responsible for the induction of TZSSIegr-I gene have been poorly characterized so far. The gene has been reported to be induced by stimulation of muscarinic, a2-adrenergic and bradykinin receptors in NG108-15 cells (Katayama et al, 1993). Our observation that 5-HT induces TISS/egr-l gene transcription and subsequently the activation of Egr-1 binding in cultured PC12 cells suggests that Egr-1 transcription factor is involved in the long-term effects evoked by this neurotransmitter.…”

Section: The Tisbiegr-1 Gene Has Neuronal Functionsmentioning

confidence: 65%

5‐Hydroxytryptamine Induces TIS8/egr‐1 and c‐fos Expression in PC12 Cells. Involvement of Tyrosine Protein Phosphorylation

Humblot

Esteve

Burgun

et al. 1997

Eur J of Neuroscience

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The TIS8/egr-1 gene is a member of the class of immediate early genes. Originally discovered as a mitogen-induced gene, it can also be induced by synaptic activity. We report here the induction of the TIS8/egr-1 gene by the neurotransmitter 5-hydroxytryptamine (5-HT) in cultured rat phaeochromocytoma PC12 cells. Induction was maximal 40 min after addition of 5-HT to the cells, and declined very rapidly to reach the basal level after 90 min. The electrophoretic mobility-shift assay showed that induction of the TIS8/egr-1 gene by 5-HT was accompained by increased Egr-1 protein binding to its DNA consensus sequence. We found an overall correlation of 5-HT-induced egr-1 expression with that of c-fos expression. The kinetics of the ability of both gene products to bind to their respective DNA consensus sequence was also similar. The 5-HT-induced activation in Egr-1 binding was inhibited by ketanserin and mesulergine, indicating that 5-HT exerted its action via a 5-HT2 receptor subtype. The tyrosine protein kinase inhibitor genistein abolished induction of the TIS8/egr-1 gene, suggesting that tyrosine kinase activity is required for the induction of early genes by 5-HT. Genistein also inhibited 5-HT-induced Egr-1 binding activity. The increase in phosphotyrosine content of focal adhesion kinase we noticed upon addition of 5-HT to cells suggests that this cytoplasmic tyrosine protein kinase mediates the effect of 5-HT in eliciting early gene induction.

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Additive Induction of Egr‐1 (zif/268) mRNA Expression in Neuroblastoma × Glioma Hybrid NG108‐15 Cells via Cholinergic Muscarinic, α₂‐Adrenergic, and Bradykinin Receptors

Cited by 16 publications

References 24 publications

Muscarinic Acetylcholine Receptors Activate Expression of the Egr Gene Family of Transcription Factors

Muscarinic Acetylcholine Receptors Activate Expression of the Egr Gene Family of Transcription Factors

Human Mas-Related G Protein-Coupled Receptors-X1 Induce Chemokine Receptor 2 Expression in Rat Dorsal Root Ganglia Neurons and Release of Chemokine Ligand 2 from the Human LAD-2 Mast Cell Line

5‐Hydroxytryptamine Induces TIS8/egr‐1 and c‐fos Expression in PC12 Cells. Involvement of Tyrosine Protein Phosphorylation

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Additive Induction of Egr‐1 (zif/268) mRNA Expression in Neuroblastoma × Glioma Hybrid NG108‐15 Cells via Cholinergic Muscarinic, α2‐Adrenergic, and Bradykinin Receptors

Cited by 16 publications

References 24 publications

Muscarinic Acetylcholine Receptors Activate Expression of the Egr Gene Family of Transcription Factors

Muscarinic Acetylcholine Receptors Activate Expression of the Egr Gene Family of Transcription Factors

Human Mas-Related G Protein-Coupled Receptors-X1 Induce Chemokine Receptor 2 Expression in Rat Dorsal Root Ganglia Neurons and Release of Chemokine Ligand 2 from the Human LAD-2 Mast Cell Line

5‐Hydroxytryptamine Induces TIS8/egr‐1 and c‐fos Expression in PC12 Cells. Involvement of Tyrosine Protein Phosphorylation

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Additive Induction of Egr‐1 (zif/268) mRNA Expression in Neuroblastoma × Glioma Hybrid NG108‐15 Cells via Cholinergic Muscarinic, α₂‐Adrenergic, and Bradykinin Receptors