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Query: UNIPROT:P05412 (c-Jun)
 11,453 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Early induction of the mRNAs encoding the c-Fos and c-Jun nuclear proteins was examined in rat brain by in situ hybridization at various timepoints following global forebrain ischemia by the method of four-vessel occlusion. All animals were subjected to 20 min of transient ischemia. This produced a pattern of proto-oncogene activation that was most intense in the granule cells of the dentate gyrus 30 min after ischemia, while the hilar cells in the dentate and the pyramidal cells of the CA3 region in the hippocampus showed a more delayed but robust expression of these immediate early genes at 1 h. The neurons of the CA1 region exhibited a more moderate hybridization signal at 1-2 h postischemia. Very little hybridization signal for either immediate early gene could be detected in animals perfused with fixative immediately following ischemia, suggesting that cellular energy levels may have to be restored to a certain level before efficient de novo mRNA synthesis can occur. In the cerebellum, a similar temporal pattern was observed: the granule cells exhibited a prompt but patchy expression of c-fos and c-jun that was followed by a delayed signal in the Purkinje cells. Without exception c-fos and c-jun appeared to be expressed in unison, although the time course of c-fos and c-jun mRNA accumulation and decay was different in various brain regions: invariably the cerebellum returned rapidly to its baseline with virtually no remaining signal at 3 h postischemia, while c-fos and c-jun activation in the hippocampus remained high at 3 h and returned to baseline by 6 h. Several other brain regions showed early production of c-fos and c-jun mRNAs, such as the medial habenula, piriform cortex, the amygdala, the centromedian, lateral posterior, paracentral, intermediodorsal and reuniens nuclei of the thalamus and the ventromedial and dorsal nuclei of the hypothalamus; in the brainstem, the trapezoid body and the noradrenergic neurons of the locus ceruleus as well as the adrenergic neurons in the ventrolateral medulla (C1 group) and nucleus tractus solitarius (C2 group) regions displayed slightly less intense hybridization signals. In addition, the ependyma of the lateral ventricles and the third ventricle showed a prompt albeit short-lived production of c-fos and c-jun mRNAs. Sham-operated animals as well as animals that had survived to one week postischemia showed either no or only trace levels of hybridization signal.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:In situ hybridization analysis of c-fos and c-jun expression in the rat brain following transient forebrain ischemia. 181 28

Fos, jun and krox belong to multigene families coding for transcription factors. These cellular immediate early genes (IEGs) are thought to be involved in coupling neuronal excitation to changes of target gene expression. Immunocytochemistry with specific antisera was used to assess regional levels of six IEG-encoded proteins (c-Fos, Fos B, Krox-24, c-Jun, Jun B, Jun D) in the rat forebrain after kainic acid-induced limbic seizures. The results demonstrate a complex spatial pattern of IEG induction and/or suppression in limbic and non-limbic structures. The sequence of induction within hippocampal subpopulations was identical for all IEGs investigated, following the order dentate gyrus, CA1 and CA3, and irrespective of different temporal profiles for individual transcription factors. Since Fos and Jun proteins act via homo- and heterodimer complexes at specific DNA sites, our data imply that the postictal combinatorial changes of these dimers allow a sequential and differential regulation of target gene expression in specific forebrain regions. Pretreatment with the non-competitive NMDA receptor antagonist MK-801 did not affect kainate-induced expression of IEGs in the limbic system, indicating that IEG induction in these regions is mediated by high-affinity kainate and AMPA receptors rather than NMDA receptors. In contrast, MK-801 abolished IEG induction in the somatosensory cortex and striatum, suggesting that IEG expression in non-limbic neurons occurs transsynaptically and is mediated by NMDA receptors.
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PMID:Spatiotemporal induction of immediate early genes in the rat brain after limbic seizures: effects of NMDA receptor antagonist MK-801. 828 3

Several studies have shown that dextromethorphan (DM) has both anticonvulsant and proconvulsant effects depending on the animal model. In this study, we examined the effects of DM on three parameters associated with kainic acid (KA)-induced seizures: cell loss in the hippocampus, increased AP-1 DNA binding activity and increased c-Jun and fos-related antigen (FRA) expression. KA administration (8 mg/kg, ip) produced robust behavioral convulsions lasting 4-6 hr. Pretreatment with DM (12.5-75 mg/kg, po) 15 min before KA injections reduced the seizures as well as mortality in a dose-dependent manner. Histological studies revealed a severe loss of cells in the CA1 and CA3 fields of the hippocampus in KA-treated rats. DM pretreatment also reduced this cell loss in a dose-dependent fashion. Biochemical studies showed that DM pretreatment also attenuated the KA-induced increase of AP-1 binding activity and c-Jun/FRA expression in the hippocampus. These results indicate that DM is an effective antagonist of KA.
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PMID:The effects of dextromethorphan on kainic acid-induced seizures in the rat. 885 34

We have previously shown that androgen receptors are found in high concentrations in hippocampal CA1 pyramidal cells. To begin to explore the possible roles for androgen receptors in this area of the brain, we studied the effects of endogenous and exogenous androgen on the behaviourally induced expression of cellular immediate early gene messenger RNAs. Adult male Fischer 344 rats were either gonadectomized, gonadectomized and given two Silastic capsules of dihydrotestosterone propionate at the time of surgery, or left intact. Three weeks later, animals were placed into a novel open field for 20 min. This behavioural paradigm caused region- and gene-specific increases of c-fos, jun-B, c-jun and zif268 messenger RNA in the hippocampus as determined by semi-quantitative in situ hybridization histochemistry. The removal of circulating androgen by gonadectomy potentiated, whereas dihydrotestosterone treatment of castrates attenuated, the behaviourally induced expression of c-fos messenger RNA in the CA1 region of the hippocampus. No changes in c-fos messenger RNA expression were detected in the CA3 or dentate gyrus regions where androgen receptor levels are low. Androgen status did not affect either the basal or stimulated expression of Jun-B, c-Jun or zif268 messenger RNA in any of the three cellular regions of the hippocampus examined. These results implicate androgen receptors in modulating the active response of hippocampal neurons to a behaviourally relevant stimulus. Since the products of cellular immediate genes can function to alter an array of downstream genes, the modulation of these genes in the hippocampus by gonadal hormones may have important ramifications for hippocampal function.
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PMID:Androgens selectively modulate C-fos messenger RNA induction in the rat hippocampus following novelty. 888 71

C-Jun expression in the hippocampus of gerbils subjected to 5 min of transient forebrain ischemia was examined with immunohistochemistry and western blotting using two c-Jun antibodies raised against two different amino acid sequences. Both c-Jun antibodies showed increased immunoreactivity at 6 and 12 h postischemia in the stratum pyramidale of CA3 and granule cell layer of the dentate gyrus. No immunostaining was detected in CA1 up to the 7th day. Western blots showed increased c-Jun immunoreactivity at 6 and 12 h. However, the antibody c-Jun (AB-1) detected a single band at about p39 in normal and post-ischemic states, whereas the antibody c-Jun/AP-1 (N) recognized a band at about p39 in normal and post-ischemic gerbils, and a p62 phosphorylated double-band at 6 and 12 h following ischemia. In addition, increased c-Jun N-terminal kinase-1 (JNK-1) expression was observed on western blots at 6 and 12 h postischemia. These results suggest that different c-Jun-related responses, some of which probably indicate post-translational changes of the c-Jun protein, occur in the hippocampus of the gerbil following transient forebrain ischemia.
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PMID:Transient forebrain ischemia in the adult gerbil is associated with a complex c-Jun response. 926 13

c-fos and c-jun mRNA induction and c-Fos and c-Jun protein expression were examined in the brains of adult rats subjected to systemic kainic acid (KA) injection at convulsant doses. Induction of c-fos and c-jun mRNA, as seen with in situ hybridization, occurred in the piriform and entorhinal cortices, neocortex, amygdala, hippocampus, dentate gyrus, and discrete thalamic nuclei. This was followed by c-Fos protein expression, as revealed with immunohistochemistry, in the same regions. However, the distribution of c-Jun protein expression differed depending on the antibody used. The distribution of cells immunostained with the antibody c-Jun (AB-1) was similar to that of c-jun mRNA, but the distribution of cells immunostained with the antibody c-Jun/AP1 (N) was restricted to a few neurons in the pyramidal cell layer of CA1 and CA3, layer II of the piriform and entorhinal cortices, basal amygdala, and discrete thalamic nuclei. Although the regional distribution of c-Fos- and c-Jun-immunoreactive cells in the hippocampus, layer II of the entorhinal and piriform cortices, basal amygdala, and discrete thalamic nuclei matched the distribution of cells committed to dying, c-Fos- and c-Jun-immunoreactive cells in the neocortex and dentate gyrus survived. Therefore, the present data show that c-fos and c-jun are not predictors of either cell death or survival, but rather, markers of cells sensitive to KA excitotoxicity. Western blots to c-Fos showed a double band at p62 in samples containing the hippocampus and entorhinal and piriform cortices (hip samples) and in samples containing the neocortex (cortex samples). The upper band was abolished following preincubation of the samples with alkaline phosphatase, thus suggesting c-Fos phosphorylation. Western blots to c-Jun (AB-1) showed a single band at about p39 in hip and cortex. However, Western blots to c-Jun/AP1 (N) identified two bands. One band at about p39 was seen in control rats and the cortex of KA-treated rats. Another band at p26 was observed only in hip samples of KA-treated rats. In addition, decreased c-Jun N-terminal kinase 1 (JNK-1) expression, as revealed on Western blots, was coincidental with the appearance of the p26 c-Jun-immunoreactive band in KA-treated rats. These results show that c-Fos and different Jun-related antigens are expressed following KA excitotoxicity, and that posttranslational modifications involving phosphorylation of c-Fos and Jun(s) may occur following KA injection. These results also stress the necessity of examining the composition of Fos and Jun-related antigens and the metabolic state of Fos and Jun(s) in different experimental models of nervous system injury.
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PMID:Kainic acid-induced excitotoxicity is associated with a complex c-Fos and c-Jun response which does not preclude either cell death or survival. 929 62

In eukaryotes, protein de novo synthesis is mainly under the control of transcription factors at the level of gene transcription in cell nuclei. Gel retardation electrophoresis was employed for determination of DNA-binding activity of the transcription factor activator protein-1 (AP1), which is a dimer between c-Fos and c-Jun protein families. Binding of a radiolabeled double-stranded oligonucleotide probe for AP1 was rapidly potentiated in the CA1 and CA3 subfields and the dentate gyrus of the hippocampus of gerbils with forebrain ischemia for 5 min. Similarly marked potentiation was seen in the thalamus and the striatum, but not in the frontal cortex, following the recirculation of blood supply. The potentiation was transient in the vulnerable CA1 subfield, but was rather persistent in the thalamus and the striatum in addition to the resistant CA3 subfield and dentate gyrus. However, administration of the neuroprotective drug bifemelane (10 to 20 mg/kg, i.p.) resulted in prolongation of the potentiation of AP1 binding in the CA1 subfield up to 6 hr after ischemia, without significantly affecting that in other central structures. Limited proteolysis revealed that bifemelane induced expression of the AP1 consisting of constructive proteins different from those expressed in control animals in the CA1 subfield. These results suggest that bifemelane may protect neuronal cells against ischemic injuries through molecular mechanisms associated with prolongation of the potentiation of AP1 binding in the vulnerable CA1 subfield after ischemia.
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PMID:Prolongation by bifemelane of potentiation of AP1 DNA binding in hippocampal CA1 subfield of gerbils with transient forebrain ischemia. 951 1

The present study has investigated the congruence of mRNA induction and protein expression of inducible transcription factors (ITFs). The patterns of c-jun, junB, c-fos, fra-1 and fra-2 mRNAs were studied by radioactive and non-radioactive in situ hybridization in the adult rat brain following kainate-induced seizure activity and axotomy. In the same animals, the expression of c-Jun, JunB and c-Fos proteins was compared with the respective mRNA signals. Using radioactive labeled probes all investigated mRNAs showed an onset within 1 h after systemic kainate application and the maximal levels were generally reached after 3 h. Each mRNA displayed a specific temporo-spatial expression pattern. Whereas fra-1 and fra-2 were restricted to the hippocampus, c-jun, junB and c-fos were additionally induced in the cortex, amygdala and thalamus. The areas with maximal labeling were the dentate gyrus and the hippocampal CA1 and CA3 subfields. The expression patterns between c-jun, junB and c-fos mRNA were virtually congruent with the respective protein. Labeling of the junB and fra-2 probes with digoxigenin yielded similar results. Twenty-four hours, 3 and 10 days following transection of the medial forebrain bundle and the mamillo-thalamic tract, high levels of c-jun mRNA (either digoxigenin or radioactive labeled probes) and protein were seen in the axotomized neurons of the substantia nigra pars compacta and mamillary body whereas the other mRNAs studied and the JunB or c-Fos proteins could not be detected. These findings demonstrate that mRNAs encoding for ITFs are translated into the respective proteins following excitotoxic seizures and axotomy, and that the antisera used for immunocytochemistry yield specific expression patterns of homologous proteins.
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PMID:Expression of c-jun, junB, c-fos, fra-1 and fra-2 mRNA in the rat brain following seizure activity and axotomy. 962 45

Transcription factors are nuclear proteins with an ability to recognize particular nucleotide sequences on double stranded genomic DNAs and thereby modulate the activity of RNA polymerase II which is responsible for the formation of messenger RNAs in cell nuclei. Gel retardation electrophoresis revealed that transient forebrain ischemia for 5 min led to drastic potentiation of binding of a radiolabelled double-stranded oligonucleotide probe for the transcription factor activator protein-1, in the thalamus as well as the CA1 and CA3 subfields and the dentate gyrus of the hippocampus of the gerbils previously given ischemia for 2 min two days before, which is known to induce tolerance to subsequent severe ischemia in the CA1 subfield. By contrast, ischemia for 5 min resulted in prolonged potentiation of activator protein-1 binding in the vulnerable CA1 subfield of the gerbils with prior ischemia for 5 min 14 days before, which is shown to induce delayed death of the pyramidal neurons exclusively in this subfield. Similar prolongation was seen with activator protein-1 binding in the vulnerable thalamus but not in the resistant CA3 subfield and dentate gyrus of the gerbils with such repeated ischemia for 5 min. Limited proteolysis by Staphylococcus aureus V8 protease as well as supershift assays using antibodies against c-Fos and c-Jun proteins demonstrated the possible difference in constructive partner proteins of activator protein-1 among nuclear extracts of the CA1 subfield obtained from gerbils with single, tolerated and repeated ischemia. These results suggest that de novo protein synthesis may underlie molecular mechanisms associated with acquisition of the ischemic tolerance through modulation at the level of gene transcription by activator protein-1 composed of different constructive partner proteins in the CA1 subfield. Possible participation of glial cells in the modulation is also suggested in particular situations.
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PMID:Possible involvement of activator protein-1 DNA binding in mechanisms underlying ischemic tolerance in the CA1 subfield of gerbil hippocampus. 969 45

We examined kainic acid (KA)-induced neuronal death and changes in glial cells in p53-deficient (p53-/-) and wild-type (p53+/+) mice which were CBA and C57BL/6 background. The p53-/- mouse exhibited a KA-induced loss of CA3 pyramidal neurons similar to that in wild-type mouse. Before neuronal death, c-Jun protein was expressed, phosphorylated and translocated into several nuclei of CA3 pyramidal neurons. In p53-/- mouse, microglial activation was slightly faster and more continuous after 1-7 days than that in p53+/+ mouse. On the other hand, p53-/- astrocytes were relatively resistant to KA cytotoxicity, and marked astrocytosis also occurred after 7 days. These observations suggest that p53-null mutation may influence the activation and proliferation of glial cells rather than neuronal death.
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PMID:Kainic acid-induced neuronal loss and glial changes in the hippocampal CA3 of p53-deficient mouse. 983 26


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