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)

Ionizing radiation produces apoptosis in the developing rat brain. Strong c-Jun immunoreactivity, as revealed with the antibody c-Jun/AP-1 (N) which is raised against the amino acids 91-105 mapping with the amino terminal domain of mouse c-Jun p39, is simultaneously observed in the nucleus and cytoplasm of apoptotic cells. Western blotting of total brain homogenates, using the same antibody, shows a p39 band in control rats which is accompanied by a strong, phosphorylated p62 double-band in irradiated animals. In addition, increased c-Jun N-terminal kinase 1 expression, as found on western blots, is found in irradiated rats when compared with controls. Intraperitoneal injection of kainic acid at convulsant doses to the adult rat produces cell death with morphological features of necrosis, together with the appearance of cells with fine granular chromatin degeneration and small numbers of apoptotic-like cells, in the entorhinal and piriform cortices, basal amygdala, certain thalamic nuclei, and CA1 region of the hippocampus. c-Jun expression in kainic acid-treated rats, as revealed with the c-Jun/AP-1 (N) antibody, is found in the nuclei of a minority of cells in the same areas. The vast majority of c-Jun-immunoreactive cells have normal nuclear morphology, whereas necrotic cells are negative and only a few cells with fine granular chromatin condensation and apoptotic cells following kainic acid injection are stained with c-Jun antibodies. Western blotting, using the same antibody, shows a p39 band in control rats, which is accompanied by a band at about p26 from 6 h onwards following kainic acid injection. Decreased c-Jun N-terminal kinase 1 expression, as revealed on western blots, is observed in kainic acid-treated rats. These results show that the antibody c-Jun/AP-1 (N) recognizes three different forms of c-Jun-related immunoreactivity in normal and pathological states, which are associated with the different outcome of cells. These results stress the necessity of examining in detail the composition of c-Jun-immunoreactive bands and the metabolic state of c-Jun(s) in different paradigms of cell death and survival.
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PMID:Radiation-induced apoptosis in developing rats and kainic acid-induced excitotoxicity in adult rats are associated with distinctive morphological and biochemical c-Jun/AP-1 (N) expression. 1068 85

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

We have examined c-Jun protein expression by immunocytochemistry in normal and pathologically induced cell death by focusing primarily on the developing neuromuscular system of the chick embryo. Several commercially available antibodies against c-Jun were used in combination with the TUNEL technique or propidium iodide staining for detection of cells undergoing programmed cell death (PCD). Among these, a rabbit polyclonal antibody raised against the amino acids 91-105 mapping to the amino terminal domain of mouse c-Jun p39 (c-Jun/sc45) transiently immunostained the cytoplasm of dying spinal cord motoneurons at a time coincident with naturally occurring motoneuron death. Late apoptotic bodies were devoid of c-Jun/sc45 immunoreactivity. A monoclonal antibody directed against a region corresponding to the amino acids 26-175 of c-Jun p39 (c-Jun/mAB) did not specifically immunostain dying neurons, but, rather, showed nuclear immunolabeling in almost all healthy motoneurons. Experimentally induced programmed death of motoneurons by means of early limb bud ablation, axotomy, or in ovo injection of the neurotoxin beta-bungarotoxin increased the number of dying cells showing positive c-Jun/sc45 immunoreactivity. Immunoelectron microscopy with c-Jun/sc45 antibody showed that the signal was present in the cytoplasm without a specific association with organelles, and was also present in large lysosome-like dense bodies inside neuritic profiles. Similar findings were obtained in different types of cells undergoing normal or experimentally induced PCD. These include dorsal root ganglion neurons, Schwann cells, muscle cells, neural tube and neural crest cells during the earliest stages of spinal cord development, and interdigital mesenchymal cells of hindlimbs. In all these cases, cells showed morphological and histochemical characteristics of apoptotic-like PCD. By contrast, motoneurons undergoing necrotic cell death induced by the excitotoxin N-methyl-D-aspartate did not show detectable c-Jun/sc45 immunoreactivity, although they displayed an increase in nuclear c-Jun/mAB immunostaining. In Western blot analysis of spinal cord extracts, c-Jun/sc45 antibody weakly detected a 39-kD band, corresponding to c-Jun, and more strongly detected two additional bands of 66 and 45 kD which followed developmental changes coincident with naturally occurring or experimentally stimulated apoptotic motoneuron death. By contrast, c-Jun/mAB only recognized a single p39 band as expected for c-Jun, and did not display changes associated with neuronal apoptosis. From these data, we conclude that the c-Jun/sc45 antibody recognizes apoptosis-related proteins associated with the early stages of morphological PCD in a variety of neuronal and non-neuronal cells, and that c-Jun/sc45 is a reliable marker for a variety of developing cells undergoing programmed cell death.
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PMID:Specific association of c-Jun-like immunoreactivity but not c-Jun p39 with normal and induced programmed cell death in the chick embryo. 1002 65

Motoneurons respond to peripheral nerve transection by either regenerative or degenerative events depending on their state of maturation. Since the expression of c-Jun has been involved in the early signalling of the regenerative process that follows nerve transection in adults, we have investigated c-Jun on rat neonatal axotomized motoneurons during the period in which neuronal death is induced. Changes in levels of c-Jun protein and its mRNA were determined by means of quantitative immunocytochemistry and in situ hybridization. Three hours after nerve transection performed on postnatal day (P)3, c-Jun protein and mRNA is induced in axotomized spinal cord motoneurons, and high levels were reached between 1 and 10 days after. This response is associated with a detectable c-Jun activation by phosphorylation on serine 63. No changes were found in the levels of activating transcription factor -2. Most of dying motoneurons were not labelled by either a specific c-Jun antibody or a c-jun mRNA probe. However, dying motoneurons were specifically stained by a polyclonal anti c-Jun antibody, indicating that some c-Jun antibodies react with unknown epitopes, probably distinct from c-Jun p39, that are specifically associated with apoptosis.
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PMID:c-Jun regulation in rat neonatal motoneurons postaxotomy. 1124 82

Cyclin-dependent kinase 5 (cdk5) is a serine/threonine kinase activated by associating with its neuron-specific activators p35 and p39. Analysis of cdk5(-/-) and p35(-/-) mice has demonstrated that both cdk5 and p35 are essential for neuronal migration, axon pathfinding and the laminar configuration of the cerebral cortex, suggesting that the cdk5-p35 complex may play a role in neuron survival. However, the targets of cdk5 that regulate neuron survival are unknown. Here, we show that cdk5 directly phosphorylates c-Jun N-terminal kinase 3 (JNK3) on Thr131 and inhibits its kinase activity, leading to reduced c-Jun phosphorylation. Expression of cdk5 and p35 in HEK293T cells inhibits c-Jun phosphorylation induced by UV irradiation. These effects can be restored by expression of a catalytically inactive mutant form of cdk5. Moreover, cdk5-deficient cultured cortical neurons exhibit increased sensitivity to apoptotic stimuli, as well as elevated JNK3 activity and c-Jun phosphorylation. Taken together, these findings show that cdk5 may exert its role as a key element by negatively regulating the c-Jun N-terminal kinase/stress-activated protein kinase signaling pathway during neuronal apoptosis.
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PMID:Cyclin-dependent kinase 5 prevents neuronal apoptosis by negative regulation of c-Jun N-terminal kinase 3. 1182 25

Acoustical or intracochlear stimulation may induce expression of the immediate early gene product c-Fos in neurons throughout the auditory brainstem. Attempting to estimate its consequences, we sought to determine if c-Fos expression occurs in neurons that also contain c-Jun p39 with which it could form the heterodimeric transcription factor AP-1 to activate a large number of genes, among them several involved in neuroplastic remodeling. Following intracochlear stimulation, c-Fos and c-Jun were found to be colocalized in nuclei of many neurons at all levels of the subcortical auditory system. We conclude that stimulation triggers Fos-Jun dimerization, causing cascades of gene expression that potentially culminate in structural changes of neurons affected by the specific pattern of activity imposed on the neuronal system.
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PMID:AP-1 activity rises by stimulation-dependent c-Fos expression in auditory neurons. 1859 6


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