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)

Ischemia and reperfusion lead to the rapid induction of proto-oncogenes in the heart and subsequent induction of genes with cardioprotective functions. The activity of the transcription factors c-Jun and ATF-2 can be stimulated by activation of c-Jun amino-terminal kinase (JNK) in response to a variety of stresses. Here we show that ischemia and reperfusion led to the activation of JNK and also of the distantly-related mitogen activated protein kinase (MAPK). Activation of JNK, but not (MAPK), was abolished by removal of calcium from the perfusate immediately prior to ischemia. In contrast, infusion of the hydrogen peroxide scavenger catalase abolished activation of MAPK in response to ischemia and reperfusion, but activation of JNK was inhibited significantly by catalase only when superoxide dismutase was also present. Hydrogen peroxide infusion activated MAPK but not JNK, supporting a role for hydrogen peroxide produced during reperfusion in MAPK activation. We conclude that while ischemia and reperfusion activate both JNK and MAPK, the mechanisms of activation are different for the 2 kinases. Activation of these kinases is likely to contribute to altered gene expression in response to ischemia and reperfusion.
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PMID:Stimulation of c-Jun kinase and mitogen-activated protein kinase by ischemia and reperfusion in the perfused rat heart. 857 81

Sensitivity to cell killing by tumor necrosis factor (TNF)-alpha was seen in the JB6-derived transformed mouse RT101 cell variants previously described as resistant to 12-O-tetradecanoylphorbol-13-acetate (TPA)-induced killing, while the TPA-sensitive variants were resistant to killing by TNF-alpha. Morphological and biochemical changes characteristic of apoptosis were found to precede TNF-alpha-induced cell death in TNF-alpha-sensitive (TNFs) but not TNF-alpha-resistant (TNFr) cells. In TNFr cells, TNF-alpha increased the cell cycle rate. The onset of cellular damage in TNFs cells, as indicated by propidium iodide uptake, was seen as early as 6 h after TNF-alpha treatment. 4,6-diamidino-2-phenylindole staining revealed chromosomal condensation approximately 4-6 h after TNF-alpha treatment. The DNA oligonucleosomal ladder of 180 bp and its multiples, a characteristic feature of apoptosis, was seen at 48 h. Little or no significant differences were found in the basal or induced levels of mRNA expression of several potential apoptosis mediator genes or apoptosis inhibitor genes. A dephosphorylated species of anti-c-Jun immunoprecipitated protein appeared in TNFs cells at 3 h posttreatment, accompanied by a parallel increase in AP-1 activity. Higher constitutive levels of the antioxidant enzymes superoxide dismutase and catalase were found in TNFr cells, but TNF-alpha did not significantly affect the activities of these enzymes or differentially induce their expression. The findings suggest that the preferential and transient increase in c-Jun dephosphorylation and AP-1 transcriptional activity may contribute to the preferential apoptotic response in TNFs cells; and that the greater constitutive oxidant defense in TNFr cells may contribute to their resistance.
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PMID:C-JUN/AP-1 as possible mediators of tumor necrosis factor-alpha-induced apoptotic response in mouse JB6 tumor cells. 874 98

Apoptotic cell death was induced in rat thymocytes on exposure to calcium ionophore A 23187 (100 micron(s)) for 24 h as observed from morphological changes and DNA fragmentation into oligonucleosomal ladder. The cell death was independent of de novo syntheses of protein. However, the involvement of c-Myc, c-Jun, poly ADPR polymerase and antioxidant enzymes CuZn SOD and catalase was observed.
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PMID:Calcium ionophore A 23187 induces apoptotic cell death in rat thymocytes. 891 72

Apoptosis is a controlled form of cell death accompanied by distinct morphological and biochemical changes. In this study the nature of cytotoxicity induced by adriamycin (ADM) in rat thymocytes was evaluated. Morphological and biochemical changes characteristic of apoptosis were found to precede adriamycin-induced cell death. Our findings demonstrate the involvement of c-Myc, c-Jun, antioxidant enzymes CuZn superoxide dismutase and catalase, and perhaps poly ADP ribosylation in ADM-induced cell death.
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PMID:Adriamycin induces apoptosis in rat thymocytes. 902 51

Exposure of mammalian cells to UV irradiation or alkylating agents leads to the activation of the c-Jun N-terminal kinase and p38 stress-activated protein kinase cascades, phosphorylation of c-Jun and ATF-2 bZIP transcription factors, and finally to selective induction of gene expression. This UV response is believed to be crucially important for cell survival, although conclusive evidence is lacking. Here, we address this issue by investigating a homologous UV response pathway in the fission yeast Schizosaccharomyces pombe. In fission yeast cells, UV irradiation induces activation of Spc1 stress-activated protein kinase, which in turn phosphorylates the Atf1 bZIP transcription factor. spc1 mutants are hypersensitive to killing by UV at a level equivalent to some checkpoint rad mutants. Whereas checkpoint rad mutants fail to arrest division in response to DNA damage, spc1 mutants are defective at resuming cell division after UV exposure. Levels of basal and UV-induced transcription of ctt1+, which encodes a catalase believed important for combating oxidative stress caused by UV, are extremely low in spc1 mutants. Atf1 is required for UV-induced transcription of ctt1+, but atf1 mutants are not hypersensitive to killing by UV. This surprising finding is explained by the observation that ctt1+ basal expression is unaffected in atf1 single mutant and spc1 atf1 double mutant cells, suggesting that unphosphorylated Atf1 represses ctt1+ expression in spc1 cells. In fact, the level of UV sensitivity of spc1 atf1 double mutant cells is intermediate between those of the wild type and spc1 mutants. These findings suggest the following. (i) Key properties of UV response mechanisms are remarkably similar in mammals and S. pombe. (ii) Activation of Spc1 kinase greatly enhances survival of UV-irradiated cells. (iii) Induction of gene expression by activation of Atf1 may not be the most important mechanism by which stress-activated kinases function in the UV response.
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PMID:Discrete roles of the Spc1 kinase and the Atf1 transcription factor in the UV response of Schizosaccharomyces pombe. 915 34

Dopamine (DA) is a neurotransmitter, but it also exerts a neurotoxic effect under certain pathological conditions, including age-related neurodegeneration such as Parkinson's disease. By using both the 293 cell line and primary neonatal rat postmitotic striatal neuron cultures, we show here that DA induces apoptosis in a time- and concentration-dependent manner. Concomitant with the apoptosis, DA activates the JNK pathway, including increases in JNK activity, phosphorylation of c-Jun, and subsequent increase in c-Jun protein. This DA-induced JNK activation precedes apoptosis and is persistently sustained during the process of apoptosis. Transient expression of a dominant negative mutant SEK1(Lys --> Arg), an upstream kinase of JNK, prevents both DA-induced JNK activation and apoptosis. A dominant negative c-Jun mutant FLAGDelta169 also reduces DA-induced apoptotic cell death. Anti-oxidants N-acetylcysteine and catalase, which serve as scavengers of reactive oxygen species generated by metabolic DA oxidation, effectively block DA-induced JNK activation and subsequent apoptosis. Thus, our data suggest that DA triggers an apoptotic death program through an oxidative stress-involved JNK activation signaling pathway. Given the fact that the anti-oxidative defense system declines during aging, this molecular event may be implicated in the age-related striatal neuronal cell loss and age-related dopaminergic neurodegenerative disorders, such as Parkinson's and Huntington's diseases.
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PMID:Dopamine induces apoptosis through an oxidation-involved SAPK/JNK activation pathway. 945 8

1. Cyclosporine A (CsA) increases eNOS mRNA expression in bovine cultured aortic endothelial cells (BAEC). As some effects of CsA may be mediated by reactive oxygen species (ROS), present experiments were devoted to test the hypothesis that the CsA-induced eNOS up-regulation could be dependent on an increased synthesis of ROS. 2. CsA induced a dose-dependent increase of ROS synthesis, with the two fluorescent probes used, DHR123 (CsA 1 microM: 305+/-7% over control) and H2DCFDA (CsA 1 microM: 178+/-6% over control). 3. Two ROS generating systems, xanthine plus xanthine oxidase (XXO) and glucose oxidase (GO), increased the expression of eNOS mRNA in BAEC, an effect which was maximal after 8 h of incubation (XXO: 168+/-21% of control values. GO: 208+/-18% of control values). The ROS-dependent increased eNOS mRNA expression was followed by an increase in eNOS activity. 4. The effect of CsA on eNOS mRNA expression was abrogated by catalase, and superoxide dismutase (SOD). In contrast, the antioxidant PDTC augmented eNOS mRNA expression, both in basal conditions and in the presence of CsA. 5. The potential participation of the transcription factor AP-1 was explored. Electrophoretic mobility shift assays were consistent with an increase in AP-1 DNA-binding activity in BAEC treated with CsA or glucose oxidase. 6. The present results support a role for ROS, particularly superoxide anion and hydrogen peroxide, as mediators of the CsA-induced eNOS mRNA up-regulation. Furthermore, they situate ROS as potential regulators of gene expression in endothelial cells, both in physiological and pathophysiological situations.
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PMID:Role of reactive oxygen species in the signalling cascade of cyclosporine A-mediated up-regulation of eNOS in vascular endothelial cells. 964 67

Cyclosporine A (CsA) and FK506 increase endothelial nitric oxide synthase (eNOS) mRNA expression in cultured bovine aortic endothelial cells (BAEC). CsA appears to increase eNOS mRNA levels mainly by increasing the rate of transcription, although a small contribution of mRNA stabilization could not be ruled out. CsA and FK506 induced an increase of ROS synthesis with the fluorescent probe used, DHR123. The ROS generating system glucose oxidase (GO) increased the expression of eNOS mRNA in BAEC. This upregulation of eNOS mRNA by CsA or GO was abrogated by catalase. As AP-1 is a redox-sensitive transcription factor and the bovine eNOS promoter has an AP-1 consensus sequence, a role of this factor in the up-regulation of eNOS mRNA was studied. Electrophoretic mobility shift assays were consistent with an increase in AP-1 DNA-binding activity in BAEC treated with CsA or glucose oxidase. The potential participation of ROS and the transcription factor AP-1 in the regulation of eNOS gene expression is suggested.
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PMID:CsA and FK506 up-regulate eNOS expression: role of reactive oxygen species and AP-1. 983 78

Drugs and certain environmental toxins may be responsible for the pathogenesis of Parkinson's disease. We have used paraquat as a model toxin for this study since paraquat has been shown to make its way to the nerve terminals and cause cell death of dopamine neurons by oxidative injury. We have shown by the electrophoretic mobility shift assay that paraquat, together with low concentrations of chelated iron (Fe++/DETAPAC), induced the activation of transcription factor AP-1 binding activity to DNA. Under similar conditions we also found by both a DNA laddering assay procedure and by terminal deoxynucleotidyl transferase assay (TUNEL assay) that paraquat also induces apoptotic cell death. Interestingly, both apoptotic cell death and AP-1/DNA binding activity induced by paraquat were blocked by cyclohexamide and genistein, indicating that both the AP-1/DNA binding activation and apoptosis induced by paraquat are closely related. Moreover, cells were also protected from paraquat toxicity in the presence of antioxidant defense enzymes SOD and catalase. The results support the hypothesis that oxidative stress may be contributing to the apoptotic cell death of dopaminergic neurons, leading to the manifestation of Parkinson's disease. Since paraquat was an important herbicide in the mid 20th Century, our results have the important implication that exposure to environmental toxins such as paraquat may induce Parkinson's disease.
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PMID:Paraquat induced activation of transcription factor AP-1 and apoptosis in PC12 cells. 1019 31

The age-related impairment in long-term potentiation in the rat dentate gyrus is coupled with an increase in the proinflammatory cytokine, interleukin-1beta (IL-1beta). It is possible that this increase in IL-1beta might be a consequence of the age-related increase in reactive oxygen species production in hippocampal tissue. In this study we set out to identify the underlying cause of the age-related increase in reactive oxygen species production and to establish whether any consequences of such a change might impact on the ability of aged rats to sustain long-term potentiation (LTP). We report that there was an age-related increase in the activity of superoxide dismutase but no parallel increases in activities of glutathione peroxidase or catalase, while age-related decreases in the concentration of the scavengers, vitamins E and C and glutathione were also observed. We propose that these compromises in antioxidative strategies may result in an increase in reactive oxygen species production. The data described indicate that IL-1beta and H2O2 increase the activity of two stress-activated mitogen-activated protein kinases, c-Jun NH2-terminal kinase (JNK) and p38 in vitro, while age-related increases in both kinases were observed. We propose that the endogenous increase in these parameters which occurs with age induces the increase in activity of the stress-activated kinases, which in turn impacts on the ability of the aged rat to sustain LTP.
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PMID:Age-related impairment in LTP is accompanied by enhanced activity of stress-activated protein kinases: analysis of underlying mechanisms. 1065 89


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