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)

Peripheral axotomy of adult rat sensory neurons causes induction of the transcription factor c-Jun and increased expression of the neuropeptides vasoactive intestinal polypeptide (VIP), galanin and neuropeptide Y. To determine whether VIP induction is dependent on transcriptional regulation by c-Jun, we exploited the fact that c-Jun and VIP are also induced in cultured sensory neurons. We blocked c-Jun synthesis by microinjecting antisense oligonucleotides and found that VIP expression, determined by quantitative immunofluorescence, was specifically reduced. Blockade of c-June expression also resulted in reduced neuropeptide Y expression but left galanin, substance P and calcitonin gene-related peptide unaffected. Since in vitro electrophoretic mobility shift assays showed that a nominal cyclic AMP responsive element (CRE) associated with the rat VIP gene could bind c-Jun-containing transcription factor complexes, we next investigated whether VIP expression in sensory neurons might depend on transcription factor binding to the CRE. When a DNA plasmid containing multiple copies of the CRE was injected into newly cultured sensory neurons to sequester transcription factors binding the endogenous CRE, there was a selective reduction in VIP expression. VIP induction in sensory neurons therefore probably results from transcriptional activation by c-Jun acting in combination with other factor(s), possibly acting through the CRE. These results show that c-Jun can regulate transcription of other genes affected by axotomy and imply that it could be a key regulator of the neuronal axotomy response.
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PMID:Regulation of VIP and other neuropeptides by c-Jun in sensory neurons: implications for the neuropeptide response to axotomy. 899 97

In adult male rats, the expression of the neuropeptide galanin and its co-localization with the c-Jun transcription factor and the NADPH-diaphorase, the marker enzyme for the nitric oxide synthase (NOS), was investigated by immunohistochemistry in axotomized neurons following unilateral stereotaxic transection of the (a) mamillo-thalamic tract, (b) medial forebrain bundle, (c) fimbria fornix bundle and (d) sciatic nerve. This surgical procedure resulted in axotomy of neurons of (a) mamillary ncl. (MnM), (b) substantia nigra compacta (SNC) and paraventricular ncl. of thalamic (PF) neurons, (c) medial septum (MS) and vertical diagonal band of Broca (VDB), and (d) sciatic motoneurons and dorsal root ganglia (DRG). In all of these axotomized neuronal subpopulations, expression of c-Jun appeared between 24 and 36 h post-axotomy and persisted on substantial levels for 15 days in the SNC and for 30-50 days in the MnM, PF, MS, VBD, sciatic DRG and motoneurons. Expression of galanin was seen in axotomized MnM, MS and DRG, but not in SNC, PF and sciatic motoneurons. Galanin-immunoreactivity (IR) appeared between 3 and 5 days after nerve fiber transection and persisted up to 50 days in the MnM, MS and DRGs. The cytoplasmic galanin-IR was almost completely restricted to those neurons showing a nuclear c-Jun expression. Moreover, galanin expression showed a long-lasting co-localization with those neurons that exhibited an increased NADPH-diaphorase reactivity in the MnM and DRG or a residual NADPH-diaphorase reactivity in MS post-axotomy. Very similar to galanin, NADPH-diaphorase was not affected by axotomy in the SNC, PF or sciatic motoneurons. Our findings suggest a common mechanism for galanin and NOS (NADPH-diaphorase activity) expression. Since the galanin promotor contains an AP-1 binding site, c-Jun might trigger the lasting induction of galanin in NOS-positive central neurons that survive the axotomy-evoked injury.
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PMID:Persisting expression of galanin in axotomized mamillary and septal neurons of adult rats labeled for c-Jun and NADPH-diaphorase. 937 52

We investigated trans-acting factors mediating galanin (GAL) gene activation by protein kinase-dependent signal transduction pathways in chromaffin cells. GAL mRNA up-regulation via the protein kinase A (PKA) pathway (25 microM forskolin) required new protein synthesis. Stimulation via protein kinase C (0.1 microM phorbol myristate acetate) did not. The involvement of activator protein-1(AP-1) and cAMP response element-binding protein (CREB) in serine/threonine protein kinase activation of GAL gene transcription was assessed. Cotransfection of a GAL reporter gene along with expression plasmids encoding c-Jun plus c-Fos, or the catalytic subunit of PKA (PKAbeta), resulted in a 4- to 8-fold enhancement of GAL reporter gene transcription. Transcriptional activation required the galanin 12-O-tetradecanoylphorbol-13-acetate (phorbol-12-myristate-13-acetate) response element (GTRE) octamer sequence (TGACGCGG) in the proximal enhancer of the GAL gene, previously shown to confer phorbol ester responsiveness in chromaffin cells. CREB coexpression did not stimulate GAL gene transcription or increase transcriptional activation by PKAbeta. The GTRE preferentially bound in vitro synthesized Jun and Fos-Jun, compared with CREB, in electrophoretic mobility shift assays. The GTRE preference for binding AP-1-immunoreactive protein compared with CREB was even more pronounced in chromaffin cell nuclear extracts, in which the majority of GTRE-bound protein in electrophoretic mobility shift assays was supershifted with anti-Fos and anti-Jun antibodies. Thus, GAL gene regulation mediated by protein kinase activation appears to involve both constitutively expressed and inducible AP-1-related proteins. Elevated potassium stimulation of GAL mRNA was completely blocked, but pituitary adenylyl cyclase-activating polypeptide and histamine stimulations were only partially blocked, by cycloheximide. Both inducible and constitutive pathways are therefore used by physiologically relevant first messengers that stimulate GAL biosynthesis in vivo.
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PMID:Both inducible and constitutive activator protein-1-like transcription factors are used for transcriptional activation of the galanin gene by different first and second messenger pathways. 1038 97

The objective of this study was to investigate whether the expression of c-Jun is involved in the neuronal response to experimental demyelination. Lysolecithin-induced demyelination was generated in two distinct neural systems in rats: in the pontocerebellar and the septohippocampal pathways. Six days after the stereotaxic injections of lysolecithin, expression of the immediate early gene c-Jun was visualized by immunohistochemistry. Lesion-specific expression of the Jun protein was observed in neurons whose axons transverse the demyelinated area. Unlike the neural response to axotomy, lysolecithin treatment did not alter the expression of the neuropeptide galanin in the septohippocampal pathway. These results suggest that c-Jun protein expression might represent one step in the neuronal response to demyelination and that this response might be distinct in its downstream events from axotomy.
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PMID:Increased c-Jun expression in neurons affected by lysolecithin-induced demyelination in rats. 1099 51

Galanin and c-jun expression after a single bladder instillation of resiniferatoxin was studied by immunocytochemistry in L6 dorsal root ganglia (DRG) neurons of the rat. The role of nerve growth factor depletion in causing that effect was also investigated. Three days after instillation of a 100 nM resiniferatoxin solution a marked increase in the number of galanin and c-Jun immunoreactive DRG cells was evident bilaterally. The increments were still present at 8 days and disappeared 1 month after treatment. Systemic administration of nerve growth factor, 100 microg/kg, prevented both overexpressions. Results suggest that the changes induced in bladder sensory neurons by intravesical resiniferatoxin are due, at least in part, to the temporary deprivation of bladder-derived neurotrophic factors, namely nerve growth factor, in those neurons.
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PMID:Nerve growth factor regulates galanin and c-jun overexpression occurring in dorsal root ganglion cells after intravesical resiniferatoxin application. 1227 May 5

Nerve injury triggers numerous changes in the injured neurons and surrounding nonneuronal cells that ultimately result in successful target reinnervation or cell death. c-Jun is a component of the heterodimeric AP-1 transcription factor, and c-Jun is highly expressed in response to neuronal trauma. Here we have investigated the role of c-jun during axonal regeneration using mice lacking c-jun in the central nervous system. After transection of the facial nerve, the absence of c-Jun caused severe defects in several aspects of the axonal response, including perineuronal sprouting, lymphocyte recruitment, and microglial activation. c-Jun-deficient motorneurons were atrophic, resistant to axotomy-induced cell death, and showed reduced target muscle reinnervation. Expression of CD44, galanin, and alpha7beta1 integrin, molecules known to be involved in regeneration, was greatly impaired, suggesting a mechanism for c-Jun-mediated axonal growth. Taken together, our results identify c-Jun as an important regulator of axonal regeneration in the injured central nervous system.
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PMID:The AP-1 transcription factor c-Jun is required for efficient axonal regeneration. 1523 11

In diabetes, peripheral nerves suffer deficient neurotrophic support-a situation which resembles axotomy. This raises the question: does inappropriate establishment of an axotomised neuronal phenotype contribute to diabetic neuropathy, and in extremis, does this provoke apoptosis? We hybridized reverse-transcribed RNA, from the dorsal root ganglia (DRG) of 8-week streptozotocin (STZ)-induced diabetic rats, to Affymetrix Rat Genome U34A chips and scanned the array for expression of (a) genes that are upregulated by axotomy, (b) proapoptotic and (c) anti-apoptotic genes. Expression of the axotomy-responsive genes coding for growth-associated protein 43 (GAP-43), galanin, neuropeptide Y (NPY), pre-pro-vasoactive intestinal polypeptide (pre-pro-VIP), neuronal nitric oxide synthase (nNOS), protease nexin 1, heat-shock protein 27 (HSP 27) and myosin light chain kinase II (MLCK II) was unaffected in ganglia from diabetic rats compared to controls; thus, no axotomised phenotype was established. The expression of the majority of proapoptotic genes in the DRG was also unaltered (bax, bad, bid, bok, c-Jun, p38, TNFR1, caspase 3 and NOS2). Similarly there was no change in expression of the majority of antiapoptotic genes (bcl2, bcl-xL, bcl-w, NfkappaB). These alterations in gene expression make it clear that neither axotomy nor apoptotic phenotypes are established in neurones in this model of diabetes.
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PMID:Expression of axotomy-inducible and apoptosis-related genes in sensory nerves of rats with experimental diabetes. 1558 61

Type 2 diabetes impairs adult neurogenesis which could play a role in the CNS complications of this serious disease. The goal of this study was to determine the potential role of galanin in protecting adult neural stem cells (NSCs) from glucolipotoxicity and to analyze whether apoptosis and the unfolded protein response were involved in the galanin-mediated effect. We also studied the regulation of galanin and its receptor subtypes under diabetes in NSCs in vitro and in the subventricular zone (SVZ) in vivo. The viability of mouse SVZ-derived NSCs and the involvement of apoptosis (Bcl-2, cleaved caspase-3) and unfolded protein response [C/EBP homologous protein (CHOP) Glucose-regulated protein 78/immunoglobulin heavy-chain binding protein (GRP78/BiP), spliced X-box binding protein 1 (XBP1), c-Jun N-terminal kinases (JNK) phosphorylation] were assessed in the presence of glucolipotoxic conditions after 24 h. The effect of diabetes on the regulation of galanin and its receptor subtypes was assessed on NSCs in vitro and in SVZ tissues isolated from normal and type 2 diabetes ob/ob mice. We show increased NSC viability following galanin receptor (GalR)3 activation. This protective effect correlated with decreased apoptosis and CHOP levels. We also report how galanin and its receptors are regulated by diabetes in vitro and in vivo. This study shows GalR3-mediated neuroprotection, supporting a potential future therapeutic development, based on GalR3 activation, for the treatment of brain disorders.
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PMID:GalR3 activation promotes adult neural stem cell survival in response to a diabetic milieu. 2392 69