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Jun Expression (jun + expression)
Selected Abstractsc-Jun Expression, activation and function in neural cell death, inflammation and repairJOURNAL OF NEUROCHEMISTRY, Issue 4 2008Gennadij Raivich Abstract Up-regulation of c-Jun is a common event in the developing, adult as well as in injured nervous system that serves as a model of transcriptional control of brain function. Functional studies employing in vivo strategies using gene deletion, targeted expression of dominant negative isoforms and pharmacological inhibitors all suggest a three pronged role of c-Jun action, exercising control over neural cell death and degeneration, in gliosis and inflammation as well as in plasticity and repair. In vitro, structural and molecular studies reveal several non-overlapping activation cascades via N-terminal c-Jun phosphorylation at serine 63 and 73 (Ser63, Ser73), and threonine 91 and 93 (Thr91, Thr93) residues, the dephosphorylation at Thr239, the p300-mediated lysine acetylation of the near C-terminal region (Lys268, Lys271, Lys 273), as well as the Jun-independent activities of the Jun N-terminal family of serine/threonine kinases, that regulate the different and disparate cellular responses. A better understanding of these non-overlapping roles in vivo could considerably increase the potential of pharmacological agents to improve neurological outcome following trauma, neonatal encephalopathy and stroke, as well as in neurodegenerative disease. [source] Injury induced c-Jun expression and phosphorylation in the dopaminergic nigral neurons of the rat: correlation with neuronal death and modulation by glial-cell-line-derived neurotrophic factorEUROPEAN JOURNAL OF NEUROSCIENCE, Issue 1 2001Elisabetta Vaudano Abstract This study was designed to determine whether induction and phosphorylation of the transcription factor c-Jun is associated with lesion-induced death of dopaminergic neurons of the substantia nigra pars compacta, and if this cellular response is modulated by glial-cell-line-derived neurotrophic factor. In adult rats, delayed dopaminergic neuron cell death induced by intrastriatal 6-hydroxydopamine injection led to a marked increase in the number of both c-Jun- and phosphorylated c-Jun-immunoreactive nuclei in the substantia nigra pars compacta. The response was maximal before any significant loss of nigral neurons could be detected (on day 7 post lesion) and was confined to the dopaminergic neurons. Similarly, 6-hydroxydopamine lesion of the striatal dopaminergic terminals or excitotoxic lesion of the striatal target neurons in neonatal rats resulted in an increased number of c-Jun- and phosphorylated c-Jun-immunoreactive nigral nuclei that preceded the loss of nigral dopaminergic neurons. By contrast, after an excitotoxic lesion of the striatal target neurons in the adult rat, resulting in atrophy but not cell death of the nigral dopaminergic neurons, no upregulation of either c-Jun or phosphorylated c-Jun was found. A single injection of 10 µg of glial-cell-line-derived-neurotrophic factor given at day 3 after the intrastriatal 6-hydroxydopamine lesion reduced the number of c-Jun- and phosphorylated c-Jun-immunoreactive nuclei in the substantia nigra and protected the dopaminergic neurons from the ensuing cell death. We conclude that c-Jun induction and phosphorylation may be involved in the cellular events leading to death of nigral dopaminergic neurons in vivo and that this response can be modulated by glial-cell-line-derived-neurotrophic factor. [source] Glomerular and tubular induction of the transcription factor c-Jun in human renal disease,THE JOURNAL OF PATHOLOGY, Issue 2 2007MH De Borst Abstract The transcription factor c-Jun regulates the expression of genes involved in proliferation and inflammation in many cell types but its role in human renal disease is largely unclear. In the current study we investigated whether c-Jun activation is associated with human renal disease and if c-Jun activation regulates pro-inflammatory and pro-fibrotic genes in renal cells. Activation of c-Jun was quantified by scoring renal expression of phosphorylated c-Jun (pc-Jun) in control human renal tissue and in biopsies from patients with various renal diseases (diabetic nephropathy, focal glomerulosclerosis, hypertension, IgA nephropathy, membranous glomerulopathy, minimal change disease, membranoproliferative glomerulonephritis, systemic lupus erythematosus, acute rejection, and Wegener's granulomatosis); this was correlated with parameters of renal damage. Furthermore, we studied the functional role of c-Jun activation in human tubular epithelial cells (HK-2) stimulated with TGF-,. Activated c-Jun was present in nuclei of glomerular and tubular cells in all human renal diseases, but only sporadically in controls. Across the diseases, the extent of pc-Jun expression correlated with the degree of focal glomerulosclerosis, interstitial fibrosis, cell proliferation, kidney injury molecule-1 (Kim-1) expression, macrophage accumulation, and impairment of renal function. In HK-2 cells, TGF-, induced c-Jun activation after 1 h (+40%, p < 0.001) and 24 h (+160%, p < 0.001). The specific c-Jun N-terminal kinase (JNK) inhibitor SP600125 abolished c-Jun phosphorylation at all time points and blunted TGF-,- or BSA-induced procollagen-1, 1 and MCP-1 gene expression in HK-2 cells. We conclude that in human renal disease, the transcription factor c-Jun is activated in glomerular and tubular cells. Activation of c-Jun may be involved in the regulation of inflammation and/or fibrosis in human renal disease. Copyright © 2007 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd. [source] Characterization of Cd-induced molecular events prior to cellular damage in primary rat hepatocytes in culture: Activation of the stress activated signal protein JNK and transcription factor AP-1JOURNAL OF BIOCHEMICAL AND MOLECULAR TOXICOLOGY, Issue 3 2004Chin-ju J. Hsiao Abstract The effect of Cadmium (Cd) on the expression of c-Jun N -terminal kinase (JNK), c-jun, and activator protein-1 (AP-1) has been investigated. We previously reported that Cd causes cell damage as indicated by increases in the cytotoxic parameters, lactate dehydrogenase and lipid peroxidation, and this damage was mediated by decreases in cellular concentration of glutathione. In the present study, we investigate the molecular events involved prior to the Cd-induced cellular toxicity and damage in primary rat hepatocytes. We propose that Cd, through the generation of reactive oxygen species (ROS) and prior to significant cellular damage, activates the stress activated signal protein JNK, regulates c-jun expression, and promotes the binding of a redox sensitive transcription factor AP-1. We show JNK activity and c-jun mRNA level significantly increased at 1 h and AP-1 DNA binding activity significantly enhanced at 3 h in the presence of 4 ,M cadmium chloride. Blocking the Cd induction of JNK activity, c-jun mRNA level, and AP-1 binding activity using the antioxidants N -acetyl cysteine (10 mM) or carnosol (0.5 ,g/mL) suggests a role for ROS. Blocking JNK activity and c-jun mRNA by SP600125 (20 ,M), a JNK inhibitor, supports the role of JNK in transmission of signals induced by Cd. © 2004 Wiley Periodicals, Inc. J Biochem Mol Toxicol 18:133,142, 2004; Published online in Wiley InterScience (www.interscience.wiley.com). DOI 10.1002/jbt.20018 [source] | ||||||||||