Glutamate, But Not Dopamine, Stimulates Stress-Activated Protein Kinase and AP-1-Mediated Transcription in Striatal Neurons

Schwarzschild, Michael A.; Cole, Rebecca L.; Hyman, Steven E.

doi:10.1523/jneurosci.17-10-03455.1997

Cited by 151 publications

(97 citation statements)

References 84 publications

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“…In contrast, dopamine (1-100 M) did not induce any significant increase in the luciferase activity (Fig. 9A), a similar result to that observed previously (Schwarzschild et al, 1997). Thus, activation of group I mGluRs can trigger AP-1-mediated transcription in living striatal cells.…”

Section: Dhpg Induces Ap-1-mediated Transcription Via the Jnk Pathwaysupporting

confidence: 89%

“…Phospho-c-Jun is a principal dimer in assembling an active transcription factor, AP-1, in striatal neurons in response to glutamate stimulation (Schwarzschild et al, 1997). Given an increased expression of phospho-c-Jun proteins after DHPG stimulation, AP-1 activity could be elevated (see below) to upregulate the AP-1-mediated transcription.…”

Section: Transactivation Of Egf Receptors Is Required For Mglur5-medimentioning

confidence: 99%

“…Agonist ligands for ionotropic glutamate receptors (NMDA or AMPA) or for group I mGluRs increased striatal ERK1/2 phosphorylation via distinct signaling mechanisms involving Ca 2ϩ -sensitive or Ca 2ϩ -insensitive kinases (Sgambato et al, 1998;Perkinton et al, 1999Perkinton et al, , 2002; Vanhoutte et al, 1999;Thandi et al, 2002;Mao et al, 2004Mao et al, , 2005aYang et al, 2004). Similarly, glutamate increased JNK phosphorylation on their Thr 183 and Tyr 185 sites in striatal neurons (Schwarzschild et al, 1997;Mukherjee et al, 1999;Vanhoutte et al, 1999;Crossthwaite et al, 2004). However, to date, the regu-lation of JNK phosphorylation by mGluRs, particularly group I receptors, has not been described in neurons.…”

Section: Introductionmentioning

confidence: 99%

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A Signaling Mechanism from Gαq-Protein-Coupled Metabotropic Glutamate Receptors to Gene Expression: Role of the c-Jun N-Terminal Kinase Pathway

Yang¹,

Mao²,

Chen³

et al. 2006

J. Neurosci.

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G␣q-protein-coupled group I metabotropic glutamate receptors (mGluRs) are densely expressed in brain neurons and are actively involved in various cellular activities. In this study, we investigated the role of group I mGluRs in regulating the c-Jun N-terminal kinase (JNK)/stress-activated protein kinase in cultured neurons. We found that selective activation of mGluR5 induced a rapid and transient phosphorylation of JNK. In a series of studies to determine the mechanisms, we found that the conventional mGluR5-associated signaling pathways (inositol-1,4,5-triphosphate-mediated Ca 2ϩ release and activation of protein kinase C) were not involved in the mGluR5 regulation. Instead, ligand stimulation of mGluR5 caused a dynamic transactivation of the epidermal growth factor (EGF) receptor, which in turn triggered a downstream signaling pathway to upregulate JNK phosphorylation. Furthermore, the mGluR5-dependent JNK activation specifically activated c-Jun, but not activating transcription factor-2 or JunD, and increased activator protein-1 (AP-1)-mediated endogenous transcriptional activity. Together, we identified a novel mGluR5-to-nucleus communication through the EGF/JNK pathway, which functions to regulate AP-1-mediated transcription.

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Section: Dhpg Induces Ap-1-mediated Transcription Via the Jnk Pathwaysupporting

confidence: 89%

Section: Transactivation Of Egf Receptors Is Required For Mglur5-medimentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

A Signaling Mechanism from Gαq-Protein-Coupled Metabotropic Glutamate Receptors to Gene Expression: Role of the c-Jun N-Terminal Kinase Pathway

Yang¹,

Mao²,

Chen³

et al. 2006

J. Neurosci.

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“…Excitatory neurotransmission through NMDA receptors usually increases intracellular Ca 2ϩ levels. It has been shown that glutamate-induced Ca 2ϩ influx into neurons activates both ERK (Fiore et al 1993b;Kurino et al 1995;Vanhoutte et al 1999;Schwarzschild et al 1999) and JNK/SAPK (Schwarzschild et al 1997) signaling pathways. In contrast, extracellular Ca 2ϩ was not required for the NMDA-receptor-mediated activation of SAPK in cultured striatal neurons (Schwarzschild et al 1999).…”

Section: Discussionmentioning

confidence: 99%

Differential and Region-Specific Activation of Mitogen-Activated Protein Kinases Following Chronic Administration of Phencyclidine in Rat Brain

Kyosseva

2001

Neuropsychopharmacology

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We have previously demonstrated elevation of the extracellular signal-regulated kinase (ERK) pathway in the cerebellum from patients with schizophrenia, an illness that may involve dysfunction of the N-methyl-D-aspartate (NMDA) receptor. Since the NMDA antagonist, phencyclidine (PCP), produces schizophrenic-like symptoms in humans, and abnormal behavior in animals, we examined the effects of chronic PCP administration in time-and dose-dependent manner on ERK and two other members of mitogen-activated protein kinase family, c-JunPhencyclidine (PCP) is a hallucinogenic drug, which in normal humans can produce psychotic reactions that resemble positive, negative, and cognitive symptoms of schizophrenia (Javitt and Zukin 1991;Javitt et al. 1999). Because of these symptoms, it is suggested that PCP might be a useful drug-induced model of schizophrenia (Thornberg and Saklad 1996;Jentsch and Roth 1999;Sams-Dodd 1999).In experimental animals, PCP produces dose-dependent increases in stereotyped behavior, locomotor activity, and ataxia. Although PCP affects multiple neurotransmitters, its main site of action is through binding to the so-called PCP receptor located within the ion channel formed by the N-methyl-D-aspartate (NMDA)-type glutamate receptor (Javitt 1987;MacDonald et al. 1990;Javitt and Zukin 1991 NO . 3 hibits NMDA receptor functioning in a noncompetitive manner. There is also substantial evidence implicating NMDA dysfunction in the pathophysiology of schizophrenia and other psychiatric illnesses (Olney and Farber 1995;Coyle 1996;Krystal et al. 1999).Several lines of evidence suggest an important role for the intracellular signal transduction pathways in the regulation of brain function, and mechanism of neural plasticity in responses to stress, antidepressant treatments and drugs of abuse (Duman et al. 1994, Duman 1998. One of these signal transduction pathways is the extracellular signal-regulated kinase (ERK) cascade, a member of the mitogen-activated protein (MAP) kinase family. This pathway converts extracellular stimuli at many cell surface receptors, such as tyrosine kinases and Gprotein coupled receptors (Marshall 1994;Crespo et al. 1994;Carraway and Carraway 1995), and ion channels associated with the NMDA-type glutamate receptors (Campos-Gonzalez and Kindy 1992;Gass et al. 1993;Kurino et al. 1995;Xia et al. 1996) to intracellular signals controlling gene expression (Guan 1994).In the ERK pathway (Figure 1), Ras-GTP activates the serine/threonine kinase Raf, which in turn phosporylates and activates MEK1 and MEK2. Activated MEK, which is a dual specificity kinase, activates ERK1 and ERK2 (p44 and p42 MAP kinase) through phosphorylation on threonine and tyrosine residues. Activated ERKs are translocated to the nucleus and phosphorylate a variety of transcription factors including Elk-1, cAMP response element binding protein (CREB) and activating transcription factor (ATF). Both ERK 1 and ERK2 are highly expressed in neurons Thomas and Hunt 1993;English and Sweatt 1997;Flood et al. 1998). They can b...

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“…However, the inhibition of ERK1/2 activation has been shown to protect a mouse neuronal cell line and rat primary cortical neurons form oxidative stress-induced neurotoxicity [1] demonstrating a possible involvement in cell death. The JNK signaling cascade has been reported to be activated by a wide range of different oxidants/reductants including hydrogen peroxide [135,218], lipid peroxidation products [6,191], different types of radiation [63], modulators of intracellular glutathione status [145], peroxynitrite [71], glutamate [180], dithiothreitol, and nitric oxide [152]. Although the links between redox status and MAPK signaling have been known for some time, data demonstrating the molecular basis of such links and identifying the sensors in this redox response are few.…”

Section: Mapk Signaling Under Oxidative Stressmentioning

confidence: 99%

MAPK signaling in neurodegeneration: influences of flavonoids and of nitric oxide

Schroeter

Boyd

Spencer

et al. 2002

Neurobiology of Aging

310

178

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Oxidative and nitrosative stress is increasingly associated with the pathology of neurodegeneration and aging. The molecular mechanisms underlying oxidative/nitrosative stress-induced neuronal damage are emerging and appear to involve a mode of death in which mitogen-activated protein kinase (MAPK) signaling pathways are strongly implicated. Thus, attention is turning towards the modulation of intracellular signaling as a therapeutic approach against neurodegeneration. Both endogenous and dietary agents have been suggested as potent modulators of intracellular signal transduction, e.g. nitric oxide and flavonoids, respectively. This review addresses recent findings on the biological effects of flavonoids and nitric oxide in neurodegeneration and aims to elucidate the rationale for their prospective use as modulators of cellular signal transduction. © 2002 Elsevier Science Inc. All rights reserved.Keywords: Apoptosis; Oxidative stress; Neuron; Flavonoids; MAP kinase; JNK; ERK; Epicatechin; Nitric oxide; Mitochondria; Redox status; Polyphenols Abbreviations: AKT, serine/threonine kinase (also known as protein kinase B); AP-1, activator protein-1; Apaf-1, apoptosis protease activating factor-1; ASK1, apoptosis signal-regulating kinase-1; Bad, Bcl-2/BclX Lassociated death promoting protein; Bax, pro-apoptotic protein of the Bcl-2 family; Bcl-2, B-cell lymphoma 2: protein with anti-apoptotic properties; BclX L , long form of Bclx: anti-apoptotic protein of the Bcl-2 family; Caspase, cysteinyl aspartic acid-protease; c-Jun, mammalian equivalent of Jun: part of the AP-1 transcription complex; CREB, cAMP response element binding protein; DIABLO/smac, mitochondria-related pro-apoptotic protein: inhibits XIAP; ERK1/2, extracellular signal-related kinase; Fas, CD95: member of the TNF receptor family; GSHST, glutathione Stransferase; JNK, c-Jun amino-terminal kinase; MAPK, mitogen-activated protein kinase; MAPKK, MAPK kinase; MAPKKK, MAPKK kinase; MEK1/2, ERK1/2-specific MAPKK; MKK4/7, JNK-specific MAPKK; MSK1, mitogen-and stress-activated kinase-1; NF-B, nuclear factor of immunoglobulin k locus in B-cells; ONOO − , peroxynitrite anion; p53, pro-apoptotic tumor suppressor gene product; PI3-kinase, phosphoinositol 3-kinase; Ras, small G-protein; RNS, reactive nitrogen species; ROS, reactive oxygen species; RSK, pp90 ribosomal S6 kinase; SAPK, stressactivated protein kinase; XIAP, X-linked inhibitor of apoptosis: inhibits the activation of caspase-9

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Glutamate, But Not Dopamine, Stimulates Stress-Activated Protein Kinase and AP-1-Mediated Transcription in Striatal Neurons

Cited by 151 publications

References 84 publications

A Signaling Mechanism from Gαq-Protein-Coupled Metabotropic Glutamate Receptors to Gene Expression: Role of the c-Jun N-Terminal Kinase Pathway

A Signaling Mechanism from Gαq-Protein-Coupled Metabotropic Glutamate Receptors to Gene Expression: Role of the c-Jun N-Terminal Kinase Pathway

Differential and Region-Specific Activation of Mitogen-Activated Protein Kinases Following Chronic Administration of Phencyclidine in Rat Brain

MAPK signaling in neurodegeneration: influences of flavonoids and of nitric oxide

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