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Query: UNIPROT:P06889 (Mol)
 630,302 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Kindling is a permanent form of brain change that results from repeated elicitation of epileptiform neural activity. c-fos has been proposed as the gene responsible for turning on molecular events that might underlie the long-term neural changes that occur during kindling. This study investigated the enhancement of c-fos levels following kindled seizures and the role of c-fos in the plastic changes underlying kindling. Male hooded rats were electrically kindled in the amygdala and the resulting c-fos and c-Ha-ras gene expression was quantified using Northern blot hybridization analysis. The results indicated that c-fos was constitutively expressed in forebrain and cerebellum, and that basal levels of c-fos were equivalent in naive and in fully kindled rats that have been seizure-free for 3 weeks. Following an amygdala-piriform kindled seizure there was a massive and transient increase in c-fos levels throughout forebrain and cerebellum. Although enhanced c-fos levels were correlated with afterdischarge (AD) duration in the kindled site, enhanced c-fos levels were also observed in the amygdala-piriform contralateral to the kindled site, and the enhancement did not depend on the occurrence of AD in the contralateral amygdala-piriform. Furthermore, electrical stimulations not resulting in AD as well as other forms of control stimulation also increased c-fos levels. We conclude that c-fos was expressed simply as a consequence of neural activity and not exclusively due to the specific neural activity or underlying plastic change required for kindling. This does not preclude a role for c-fos in the long-term response to external stimuli, but it does suggest that c-fos is not the crucial 'master switch' in turning on a molecular program that might underlie kindling.
Brain Res Mol Brain Res 1991 Aug
PMID:Expression of the proto-oncogene c-fos following electrical kindling in the rat. 166 40

Previous studies have shown that stimulation of adrenergic receptors in the brain increases the expression of the immediate early gene (IEG), c-fos, in vivo (Mol. Brain Res., 6(1989) 39-45). The present study was undertaken to determine whether this also holds for other IEGs which have been shown to be activated in brain cell culture by adrenergic agonists. Both yohimbine injection and stressful stimulation, two treatments causing brain norepinephrine (NE) release, were found to cause a parallel, transient activation of at least 5 IEGs (c-fos, nur77, tis-7, zif-268 and tis-21) in the rat cortex. Genes that are not immediate early (beta-actin, NGF and HSP70) were found not to be affected in the interval used (6 h). The responses were mediated predominantly by beta-adrenoceptors with some contribution from alpha 1 receptors. The parallel activation of multiple genes by noradrenergic receptors may enable the coding of different biochemical responses to the activation of different receptors.
Brain Res Mol Brain Res 1991 Aug
PMID:Noradrenergic activation of immediate early genes in rat cerebral cortex. 166 44

The biochemical alterations eliciting the growth and spread of afterdischarge and accompanying the evolution of behavioral seizure stages in electrical kindling are not known. In situ hybridization for c-fos mRNA was used to map potential brain structures recruited during the evolution of major seizures from electrical kindling of the amygdala in rats. Two different patterns of c-fos induction were observed in the earliest stages of kindling (stages 1 and 2). A unilateral cortical distribution included the insular, temporal, perirhinal and parietal cortices and the amygdala. No changes in the hippocampus were noted in this group. The second distribution pattern was limited to the hippocampus (either unilateral or bilateral) and amygdala (unilateral) with no changes in the cortical areas. The afterdischarge durations were significantly (2 fold) longer in the 'hippocampal' group as compared to the 'cortical' group. In the later stages of kindling (stages 4 and 5) the distribution of c-fos mRNA was uniformly bilateral and involved a combination of the hippocampal and cortical distributions observed in the earlier stages and including the amygdala bilaterally as well. The induction of c-fos mRNA appears to provide a map of two different routes in the sequential pathways involved in the evolution of kindled seizures; it may also ultimately prove to be an important component of the kindling process itself. Additionally, c-fos mRNA was elevated bilaterally in the inferior colliculus of animals exhibiting running fits with their seizures. The inferior colliculus was previously shown by others to be involved in running fits accompanying convulsions.
Brain Res Mol Brain Res 1991 Aug
PMID:Regional expression of c-fos mRNA in rat brain during the evolution of amygdala kindled seizures. 166 46

In the present study we examined the relationship between the induction of long-term potentiation (LTP) in the dentate gyrus of anesthetized rats and activation of immediate early genes (IEGs; c-fos and zif/268) using several different high-frequency stimulation paradigms. Stimulation parameters that effectively induced LTP were not associated with IEG activation. Conversely, stimulation parameters that failed to induce LTP consistently resulted in IEG activation. These results suggest that there is a negative correlation between IEG activation and LTP, and that activation of IEGs is neither necessary nor sufficient for the induction of LTP.
Brain Res Mol Brain Res 1991 Aug
PMID:A negative correlation between the induction of long-term potentiation and activation of immediate early genes. 166 48

CRF is a potent hypophysiotropic factor which stimulates POMC-producing cells in both the intermediate and anterior pituitary. Although its secretagogue effects and its stimulatory action on POMC gene expression are well documented, the mechanisms by which CRF modulates gene regulation are poorly understood. In this study we have investigated the mechanisms by which CRF stimulates the immediate early gene c-fos. Studies were performed in the corticotroph-derived AtT20 cell line. We show that CRF induces a transient increase in c-fos mRNA levels. This induction is reduced by blockade of calcium entry and by calmodulin inhibitors, suggesting that the CRF-induced c-fos increase is mediated in part by the second messenger Ca2+ and the Ca2+/calmodulin kinase. When protein kinase-A (PKA) was inhibited by introduction of a mutated regulatory subunit of PKA that lacks cAMP-binding sites, the stimulation of c-fos mRNA by CRF was abolished. Taken together, these results suggest that CRF activates the c-fos protooncogene via PKA and the Ca2+/calmodulin kinase. These results were confirmed and extended by gene transfer studies using chimera genes containing c-fos promoter sequences coupled to the chloramphenicol acetyl transferase reporter gene. This series of experiments shows that CRF stimulates c-fos transcription by mechanisms requiring PKA activation. Furthermore, cotransfection experiments with the POMC promoter linked to the chloramphenicol acetyl transferase reporter gene along with an expression vector coding for cFOS showed efficient stimulation of POMC gene transcription by cFOS. In summary, c-fos mRNA accumulation is an early genomic signal in pituitary cells in response to CRF, and cFOS may represent a signal controlling POMC gene expression.
Mol Endocrinol 1991 Sep
PMID:The protooncogene c-fos is induced by corticotropin-releasing factor and stimulates proopiomelanocortin gene transcription in pituitary cells. 166 13

Induction of the c-fos gene is well known to be transient, due to autorepression of its transcription. While the dyad symmetry element (DSE) in the c-fos promoter has been shown to mediate transient c-fos transcription in response to serum, it is yet unknown whether the cAMP response elements (CREs) in the promoter mediate transient transcription in response to cAMP. We observed that forskolin induced transient expression of the c-fos gene in the presence of a calcium ionophore A23187 in NIH3T3 fibroblasts. We investigated transcriptional abilities of one of the CREs (-60 CRE) as well as the DSE. Both of the elements mediated the synergistic effects of forskolin and A23187 on transcription. Transcription driven by the -60 CRE was downregulated at around 2 hrs. after stimulation of forskolin plus A23187 with similar kinetics to that by the DSE. The downregulation with the -60 CRE was less sensitive to an inhibitor of protein synthesis comparing with that by the DSE. These results suggest that function of the -60 CRE activated by forskolin plus A23187 is downregulated by activation of pre-existing factors.
Cell Mol Biol 1991
PMID:Rapid downregulation of transcription mediated by the cAMP response element of c-fos promoter does not require new protein synthesis. 166 80

We have examined the expression of the extracellular matrix-degrading metalloprotease transin/stromelysin during the early phases of rat liver regeneration following toxic injury by a single dose of carbon tetrachloride (CCl4). In situ hybridization displayed cell type-specific spatial and temporal RNA expression patterns with high transcript levels in small proportions of hepatocytes and non-parenchymal cells, peaking at 24 and 48 h after intoxication, respectively. In agreement with the presence of c-fos and c-jun recognition sites on the transin gene, expression of these oncogenes preceded transin expression. Transin-expressing hepatocytes were largely localized in areas subsequently eliminated by necrosis due to CCl4 intoxication. As a consequence of these expression patterns and the key function of transin as an activator of interstitial collagenase, it seems that the hepatic fibrosis observed after CCl4 administration may be related to fibrogenesis unbalanced by fibrolysis due to altered transin expression.
Virchows Arch B Cell Pathol Incl Mol Pathol 1991
PMID:Temporal and spatial patterns of transin/stromelysin RNA expression following toxic injury in rat liver. 168 36

The AP1 transcriptional complex is a heterodimer composed of proteins encoded by the fos and jun proto-oncogene families. Changes in the concentration and composition of AP1 occur after cells are perturbed in a variety of different ways (Curran, in Reddy et al., eds. "The Oncogene Handbook," Amsterdam: Elsevier, pp 307-325, 1988; Sonnenberg et al., Neuron 3:359-365, 1989). Transient changes in AP1 content presumably result in altered expression of AP1-regulated target genes, that help to mediate the cell's long-term response to changes in its environment. One factor that may be important in determining which target genes are regulated by AP1 in a given context is the identity of the jun family member present in the complex (Chiu et al., Cell 59:979-986, 1989; Schutte et al., Cell 59:987-997, 1989). Fos induction has been demonstrated after binding of beta-adrenergic ligands to their cell surface receptors (Barka et al., Mol Cell Biol 6:2984-2989, 1986; Gubits et al., Mol Brain Res 6: 39-45, 1989; Arenander et al., J Neurosci Res 24: 107-114, 1989; Mocchetti et al., Proc Natl Acad Sci USA 86:3891-3895, 1989). However, the response of the jun gene family to this treatment has not been reported. We have therefore examined the effect of beta-adrenergic receptor activation on the expression of c-fos, c-jun, and junB mRNA levels in C6 glioma cells. Our results indicate that c-fos and junB mRNA levels are increased by 52- and 2.7-fold, respectively, after 45 min of isoproterenol (IPR) treatment.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Beta-adrenergic treatment of C6 glioma cells produces opposite changes in c-fos and c-jun mRNA levels. 168 82

Immediate early genes (IEGs) are a class of genes that show rapid and transient but protein synthesis-independent increases in expression to extracellular signals such as growth factors and neurotransmitters. Many IEGs code for transcription factors that have been suggested to govern the growth and differentiation of many cell types by regulating the expression of other genes. IEGs are expressed in adult neurons both constitutively and in response to afferent activity, and it has been suggested that during learning, IEGs may play a role in the signal cascade, resulting in the expression of genes critical for the consolidation of long-term memory. Long-term potentiation (LTP) is a persistent, activity-dependent form of synaptic plasticity that stands as a good candidate for the mechanism of associative memory. A number of IEGs coding for transcription factors have been shown to transiently increase transcription in the dentate gyrus of rats following LTP-inducing afferent stimulation. These include zif/268 (also termed NGFI-A, Krox-24, TIS-8, and egr-l), c-fos-related genes, c-jun, junB, and junD. Of these, zif/268 appears to be the most specifically related to LTP since it is evoked under virtually all LTP-inducing situations and shows a remarkably high correlation with the duration of LTP. There are a number of outstanding questions regarding the role of zif/268 and other IEGs in LTP, including which second messenger systems are important for activating them, which "late effector" genes are regulated by them, and the exact role these genes play, if any, in the stabilization and maintenance of LTP.
Mol Neurobiol 1991
PMID:The role of immediate early genes in the stabilization of long-term potentiation. 168 55

Several lines of evidence have suggested that c-fos may act downstream from c-Ha-ras in a growth-regulatory signal transduction pathway. We used antisense RNA to inhibit c-fos gene expression and investigated the effects of diminished c-fos expression on the phenotypes induced by the EJ c-Ha-ras oncogene in NIH 3T3 cells. Immunofluorescent staining demonstrated that the antisense RNA caused a marked reduction in the amount of c-fos protein expressed following serum stimulation. EJ cells containing antisense-fos RNA continued to overexpress ras and remained capable of proliferating in vitro. However, the antisense-fos RNA caused a partial reversion of the major transformed phenotypes of EJ cells, including a restoration of both density-dependent growth arrest and the ability to be rendered quiescent by serum deprivation, a reversion to a flat morphology, inhibition of anchorage-independent growth, and inhibition of tumorigenicity in nude mice. Our results indicate that inhibition of c-fos expression, to a level still supporting in vitro proliferation, prevents the transforming effects of the ras oncogene; they thus provide additional evidence for the participation of c-fos in ras-regulated signal transduction pathways.
Mol Cell Biol 1990 Apr
PMID:Antisense-fos RNA causes partial reversion of the transformed phenotypes induced by the c-Ha-ras oncogene. 169 Aug 47


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