Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P05412 (c-Jun)
 11,453 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

delta-9-Tetrahydrocannabinol (THC) is a major psychoactive component of cannabis. We have recently localized a receptor for THC in the forebrain and found in the caudate-putamen that its gene expression is modulated by glucocorticoids, dopamine and glutamate. Here, we report for the first time, using quantitative in situ hybridization, that acute THC (5 mg kg-1, i.p.) regulates the mRNA levels of multiple immediate early genes in the adult rat forebrain. Twenty minutes after a single THC injection, significant increases in concentration of the mRNAs for C-FOS, C-JUN and ZIF-268 were observed in the cingulate cortex (75, 45 and 37%) and for C-FOS and ZIF-268 in the fronto-parietal cortex (60 and 64%) and caudate-putamen (81 and 32%) while JUN-D mRNA levels were not changed. These transcription factor genes might mediate putative THC modulation of neurotransmitter gene expression.
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PMID:Activation of multiple transcription factor genes by tetrahydrocannabinol in rat forebrain. 791 80

After inhalation of 15% CO2, immunoreactions to glutamate and glutamic acid decarboxylase were found in some c-Fos or c-Jun-labeled neurons distributed in the reticular region just dorsal to the pyramidal tract in the rostroventromedial medulla (parapyramidal RVMM). This region forms vertically the narrow strip between the nucleus raphe pallidus and nucleus parapyramidalis superficialis, and extends rostrocaudally from the level just ahead of the inferior olivary complex to the level just behind the nucleus of the trapezoid body. When we placed lesions with kainate in the parapyramidal RVMM, hyperpneic and tachypneic responses to brief inhalation of 15% CO2 were completely abolished, and the eupneic rhythm changed into the gasping rhythm. This study suggests that the parapyramidal RVMM consists of neuronal substrates that subserve as the respiratory rhythm modulator.
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PMID:Parapyramidal rostroventromedial medulla as a respiratory rhythm modulator. 874 42

The significance of mild hypothermia as a therapeutic measure for ischemic brain damage is presented on the basis of different experimental results. An extracellular glutamate surge, a sustained activation of N-methyl-D-aspartate (NMDA) receptors, and an enhancement of DNA binding activity to transcription factor AP-1, all being key items directly linked to excitotoxic neuronal damage, are deeply affected by slightly lowering temperature (mild hypothermia [MH]). The cellular mechanism of MH seems rather nonspecific but tends to collectively involve these key items rendering neurons resistant to ischemic damage. Clinical application of MH should be a great challenge to relieve deadly effects on central neurons.
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PMID:Ischemic neuronal damage. How does mild hypothermia modulate it? 887 59

Drugs that stimulate dopamine and glutamate receptors have been shown to induce the expression of AP-1 proteins (such as c-Fos and c-Jun) in the striatum and to induce binding of these proteins to AP-1 sites on DNA, leading to the hypothesis that AP-1-mediated transcription contributes to the long-term effects of these drugs. To examine this hypothesis, we compared the regulation of AP-1-mediated transcription to the inductions of AP-1-binding activity and genes encoding AP-1 proteins in primary cultures of striatal neurons. Although glutamate, dopamine, and forskolin (an activator of adenylate cyclase) all induce c-fos mRNA and AP-1 binding, we found, surprisingly, that only glutamate induces transcription of a transfected AP-1-driven fusion gene. To explore the basis for this discrepancy, we investigated the possibility that the phosphorylation of c-Jun may also be required for AP-1-mediated transcription in striatal neurons. Glutamate, but neither dopamine nor forskolin, raises the levels of phosphorylated c-Jun as well as the activity of a Jun kinase (SAPK/JNK) in striatal cultures. Both the glutamatergic induction of AP-1-mediated transcription and activation of SAPK/JNK appear to be mediated, at least in part, via NMDA receptors. In striatal neurons, the phosphorylation of AP-1 proteins produced by glutamate may be required to convert AP-1 protein expression and binding to transcriptional activation.
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PMID:Glutamate, but not dopamine, stimulates stress-activated protein kinase and AP-1-mediated transcription in striatal neurons. 913 71

Effects of the glutamate receptor agonists, N-methyl-D-aspartate (NMDA) and alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA), on the activator protein-1 (AP-1) DNA binding activity were studied in primary cultures of rat cerebellar granule cells. Application of NMDA as well as of AMPA produced a concentration-dependent enhancement of AP-1 binding. Further examination revealed that only a brief exposure (10 min) to NMDA or AMPA was required for the initiation of a significant, four- to sixfold enhancement of AP-1 DNA binding activity. Blockade of the desensitization of AMPA receptors by cyclothiazide further reduced the exposure time needed to activate the AP-1 complex. The time needed to achieve a maximal increase of AP-1 binding activity varied depending on the glutamate receptor agonist used. NMDA gave maximal AP-1 stimulation after 60 min exposure, whereas stimulation with AMPA alone reached a maximum after 240 min exposure. When AMPA was applied together with cyclothiazide the maximal enhancement of AP-1 binding was reached much faster, within 120 min. Supershift analysis with specific antibodies against the members of Fos and Jun protein families (c-Fos, Fos B, c-Jun, Jun B, Jun D) revealed that the NMDA-induced AP-1 complex was composed predominantly of Jun D and c-Fos. The composition of the AP-1 complex activated by AMPA alone was similar to that produced by NMDA, but with an additional contribution of Fos B. In contrast, application of AMPA plus cyclothiazide induced an AP-1 transcription with contribution of Jun D, c-Fos, Fos B, c-Jun and Jun B proteins. These findings indicate that glutamate is able to enhance AP-1 DNA binding activity in cerebellar granule cells through both NMDA and AMPA glutamate receptors.
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PMID:Characterization of NMDA- and AMPA-induced enhancement of AP-1 DNA binding activity in rat cerebellar granule cells. 913 62

Cerebellar granule neurons cultured with serum develop a mature neuronal phenotype, including stimulus-coupled release of glutamate, and depend on elevated potassium for survival. We find that cells cultured with serum undergo two phases of cell death. By 6 d in vitro, 30-50% of the cells present are dead; after this time the remaining cells die. Elevated potassium prevents only this later phase of death, whereas neurotrophins protect these cells against the early phase of death. Factors that bind p75(NTR) or TNF-R, members of the same receptor family, exhibit voltage-sensitive calcium channel-dependent protection, whereas ligands of expressed Trk receptors show additional calcium channel-independent protection. The cells express TrkB protein and show elevated c-Fos and c-Jun levels in response to BDNF. No TrkA is detected, although p75(NTR) protein is expressed and NGF induces depolarization-dependent elevation of c-Jun levels. In the presence of the protein kinase C inhibitor bisindolylmaleimide, BDNF-induced survival promotion is reduced partially, whereas NGF-induced death is unmasked. Basal survival mechanisms are insensitive to inhibition of PK-C or PI-3 kinase. We conclude that BDNF promotes survival in part via its TrkB receptor, whereas there is an additional pathway promoting survival and elevating c-Jun evoked by both NGF and BDNF via a non-Trk receptor.
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PMID:Neurotrophins protect cultured cerebellar granule neurons against the early phase of cell death by a two-component mechanism. 915 37

An excessive neuronal stimulation through glutamate receptors is known to result in excitotoxic cell death of apoptotic (programmed) character. Granule cells of hippocampal dentate gyrus are believed to be particularly resistant to excitotoxic insults, despite the fact that pyramidal neurons of the hippocampus proper are apparently the most vulnerable brain cells. In this study, we report that neurons derived from the rat 5-day-old dentate gyrus, and maintained in vitro for 6 days, may undergo apoptosis after treatment with L-glutamate, in a dose-dependent manner-with up to 80% of neurons displaying features of programmed cell death after 24 h exposure to 0.5 mM glutamate. This conclusion is based on morphological evaluation of the cultures, nuclear staining with Hoechst 33258 and acridine orange revealing chromatin abnormalities, as well as terminal transferase labeling of DNA fragmentation. Since apoptosis is believed to be an active process involving gene expression, immunocytochemical of c-Fos and c-Jun transcription factor proteins was performed. Elevated expression of both proteins was found to follow quickly (within 1 h) after addition of glutamate. However, this effect was not dose-dependent, thus it does not provide clear correlations to the programmed cell death. In conclusion, this study reports on the establishment of a novel apoptotic model of excitotoxicity, and invites further efforts to investigate a basis for in vitro susceptibility and in vivo resistance of dentate gyrus granule cells to excitotoxic insult evoking apoptosis.
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PMID:Cellular and molecular correlates of glutamate-evoked neuronal programmed cell death in the in vitro cultures of rat hippocampal dentate gyrus. 922 Apr 55

Excitatory amino acids induce both acute membrane depolarization and latent cellular toxicity, which often leads to apoptosis in many neurological disorders. Recent studies indicate that glutamate toxicity may involve the c-Jun amino-terminal kinase (JNK) group of mitogen-activated protein (MAP) kinases. One member of the JNK family, Jnk3, may be required for stress-induced neuronal apoptosis, as it is selectively expressed in the nervous system. Here we report that disruption of the gene encoding Jnk3 in mice caused the mice to be resistant to the excitotoxic glutamate-receptor agonist kainic acid: they showed a reduction in seizure activity and hippocampal neuron apoptosis was prevented. Although application of kainic acid imposed the same level of noxious stress, the phosphorylation of c-Jun and the transcriptional activity of the AP-1 transcription factor complex were markedly reduced in the mutant mice. These data indicate that the observed neuroprotection is due to the extinction of a Jnk3-mediated signalling pathway, which is an important component in the pathogenesis of glutamate neurotoxicity.
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PMID:Absence of excitotoxicity-induced apoptosis in the hippocampus of mice lacking the Jnk3 gene. 934 20

Studies of programmed cell death in the developing retina in vitro are currently reviewed. The results of inhibiting protein synthesis in retinal explants indicate two mechanisms of apoptosis. One mechanism depends on the synthesis of positive modulators ('killer proteins'), while a distinct, latent mechanism appears to be continuously blocked by negative modulators. Extracellular modulators of apoptosis include the neurotrophic factors NT-4 and BDNF, while glutamate may have either a positive or a negative modulatory action on apoptosis. Several protein kinases selectively modulate apoptosis in distinct retinal layers. Calcium and nitric oxide were also shown to affect apoptosis in the developing retinal tissue. The protein c-Jun was found associated with apoptosis in various circumstances, while p53 seems to be selectively expressed in some instances of apoptosis. The results indicate that the sensitivity of each retinal cell to apoptosis is controlled by multiple, interactive, cell type- and context-specific mechanisms. Apoptosis in the retina depends on a critical interplay of extracellular signals delivered through neurotrophic factors, neurotransmitters and neuromodulators, several signal transduction pathways, and the expression of a variety of genes.
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PMID:Death in a dish: controls of apoptosis within the developing retinal tissue. 939 92

Axon sprouting in dentate granule cells is an important model of structural plasticity in the hippocampus. Although the process can be triggered by deafferentation, intense activation of glutamate receptors, and other convulsant stimuli, the specific molecular steps required to initiate and sustain mossy fiber (MF) reorganization are unknown. The cellular immediate early genes (IEGs) c-fos, c-jun, and zif/268 are major candidates for the initial steps of this plasticity, because they encode transcription factors that may trigger cascades of activity-dependent neuronal gene expression and are strongly induced in all experimental models of MF sprouting. The mutant mouse stargazer offers an important opportunity to test the specific role of IEGs, because it displays generalized nonconvulsive epilepsy and intense MF sprouting in the absence of regional cell injury. Here we report that stargazer mice show no detectable elevations in c-Fos, c-Jun, or Zif/268 immediate early gene proteins (IEGPs) before or during MF growth. Experimental results in stargazer, including (1) a strong IEGP response to kainate-induced convulsive seizures, (2) no IEGP response after prolongation of spike-wave synchronization, (3) no IEGP increase at the developmental onset of seizures or after prolonged seizure suppression, and (4) unaltered levels of the intracellular Ca2+-buffering proteins calbindin-D28k or parvalbumin, exclude the possibility that absence of an IEGP response in stargazer is either gene-linked or suppressed by known refractory mechanisms. These data demonstrate that increased levels of these IEGPs are not an obligatory step in MF-reactive sprouting and differentiate the early downstream molecular cascades of two major seizure types.
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PMID:Nonobligate role of early or sustained expression of immediate-early gene proteins c-fos, c-jun, and Zif/268 in hippocampal mossy fiber sprouting. 980 64


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