Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UNIPROT:P05412 (c-Jun)
 11,453 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Single ultraviolet (u.v.) irradiation of mammalian cells in culture evokes the transcriptional activation of various proto-oncogenes, among them members of the fos/jun family which are known to play an important role in cell proliferation and differentiation. u.v. exposure of mammalian skin results in growth arrest and cell death followed by hyperproliferation of epidermal cells. To obtain information in vivo about a possible relationship between u.v.-induced proto-oncogene expression and cellular alterations, we have analysed the expression of c-fos, fosB, c-jun, junB, bcl-2 and bax in rat epidermis after single and chronic u.v. irradiation. We present data demonstrating that the transcripts of these genes are constitutively expressed in the epidermis and that expression is differentially modulated by u.v. exposure. Single u.v. irradiation causes a rapid and sustained increase in c-jun, junB and c-fos mRNA and a decline in bcl-2 transcripts, whereas expression of bax remained unchanged. c-Fos and c-Jun immunoreactivity was localized throughout the epidermal cell layers 1.5 h after single irradiation, but restricted to basal cells at 48 h suggesting an involvement in both u.v.-induced apoptosis and hyperproliferation. 48 h after chronic exposure a significantly higher induction and a totally different pattern of epidermal proto-oncogene expression was detectable which may be associated with malignancy. Superfusion of rat skin with c-fos antisense oligodeoxynucleotides inhibited the increase in c-Fos immunolabeled epidermal cells 1.5 h after single u.v. irradiation demonstrating that antisense oligodeoxynucleotides are capable of penetrating mammalian skin and modulating the u.v. response in vivo. However, suppression of the early c-Fos activation did not significantly affect the formation of sunburn cells in the u.v.-exposed epidermis. Thus, c-Fos does not seem to play a major role in u.v.-induced apoptosis or other members of the fos/jun family may compensate for a loss in c-Fos.
 ...
PMID:Differential regulation of c-fos, fosB, c-jun, junB, bcl-2 and bax expression in rat skin following single or chronic ultraviolet irradiation and in vivo modulation by antisense oligodeoxynucleotide superfusion. 793 45

The RRR-alpha-tocopheryl succinate form of vitamin E [vitamin E succinate (VES)] inhibits the proliferation of avian reticuloendotheliosis virus-transformed RECC-UTC4-1 (C4-1) lymphoblastoid cells in a dose-dependent manner, blocks the cells in the G2/M cell cycle phase, and induces the cells to undergo apoptosis. Apoptosis was documented by demonstrating changes that are characteristic of this type of cell death, including morphological analyses of chromatin condensation by 4',6-diamidine-2'-phenylindole dihydrochloride (DAPI) staining using scanning confocal and traditional fluorescent microscopy; flow cytometry analyses of propidium iodide-labeled DNA showing fragmented DNA as a pre-G1 peak; two-color flow cytometry analyses of intact cells labeled first by the TUNEL procedure (terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate-biotin nick-end-labeled DNA stained with fluorescein isothiocyanate-labeled avidin) and then by propidium iodide demonstrating fragmented DNA; and electrophoresis of DNA showing a DNA ladder created by internucleosomal DNA fragmentation. The percentage of apoptotic cells was determined by DAPI staining and showed 11%, 27%, and 49% of cells to be apoptotic after treatment with 10 micrograms/ml VES for one, two, and three days, respectively. Analyses of mRNA levels of genes that have been implicated in the apoptotic process, namely, bcl-2, c-myc, and c-jun, revealed no change in bcl-2, decreases in c-myc mRNA levels after 36 hours of treatment, and increases in c-jun mRNA levels within four hours after treatment. Western immunoblotting analyses of protein levels for the transcription factors c-Myc and c-Jun showed normal levels of c-Myc at early time points and decreased levels at 24 and 48 hours after treatment. c-Jun increased as early as 6 hours after treatment and returned to lower (yet still elevated over control) levels by 48 hours. To determine possible functional consequences of increased c-Jun expression, gel electrophoretic mobility assays were conducted that showed increased AP-1 binding at 24 and 48 hours after treatment. These data show that VES induces apoptosis in reticuloendotheliosis virus-transformed lymphoid cells and suggest that decreases of c-Myc protein and increases of c-Jun protein and DNA binding capacity may be playing a role in VES-mediated events leading to apoptosis in this cell type.
 ...
PMID:RRR-alpha-tocopheryl succinate induces apoptosis in avian retrovirus-transformed lymphoid cells. 883 58

Inhibitors of interleukin-1beta converting enzyme (ICE) and a related group of cysteine aspartases of the ICE/ced-3 family inhibit cell death in a variety of settings, including in PC12 cells and sympathetic neurons following withdrawal of trophic support. To assess the particular member(s) of the ICE/ced-3 family that are relevant to cell death and to position their activation within the apoptotic pathway, we have used specific substrates to measure ICE-like and CPP32-like enzymatic activity in naive and neuronally differentiated PC12 cells that had been deprived of trophic support (nerve growth factor and/or serum). Rapid induction of CPP32-like, but not ICE-like, activity was observed. c-Jun kinase activation and the action of bcl-2 and other survival agents, such as cell cycle blockers, a NO generator, N-acetylcysteine, aurintricarboxylic acid, and actinomycin D occurred at a point further upstream in the apoptotic pathway compared with the aspartase activation. In living cells, zVAD-FMK, a pseudosubstrate aspartase inhibitor, blocked the activity/activation of the aspartase at concentrations about one order of magnitude lower than those required to promote survival, raising the possibility that the CPP32-like aspartase is not the main death effector in this model.
 ...
PMID:Induction of CPP32-like activity in PC12 cells by withdrawal of trophic support. Dissociation from apoptosis. 894 42

RRR-alpha-tocopheryl succinate (vitamin E succinate, VES) treatment of murine EL4 T lymphoma cells induced the cells to undergo apoptosis. After 48 hours of VES treatment at 20 micrograms/ml, 95% of cells were apoptotic. Evidence for the induction of apoptosis by VES treatments is based on staining of DNA for detection of chromatin condensation/fragmentation, two-color flow-cytometric analyses of DNA content, and end-labeled DNA and electrophoretic analyses for detection of DNA ladder formation. VES-treated EL4 cells were blocked in the G1 cell cycle phase; however, apoptotic cells came from all cell cycle phases. Analyses of mRNA expression of genes involved in apoptosis revealed decreased c-myc and increased bcl-2, c-fos, and c-jun mRNAs within three to six hours after treatment. Western analyses showed increased c-Jun, c-Fos, and Bcl-2 protein levels. Electrophoretic mobility shift assays showed increased AP-1 binding at 6, 12, and 24 hours after treatment and decreased c-Myc binding after 12 and 24 hours of VES treatment. Treatments of EL4 cells with VES+RRR-alpha-to-copherol reduced apoptosis without effecting DNA synthesis arrest. Treatments of EL4 cells with VES+rac-6-hydroxyl-2, 5,7,8-tetramethyl-chroman-2-carboxylic acid, butylated hydroxytoluene, or butylated hydroxyanisole had no effect on apoptosis or DNA synthesis arrest caused by VES treatments. Analyses of bcl-2, c-myc, c-jun, and c-fos mRNA levels in cells receiving VES + RRR-alpha-tocopherol treatments showed no change from cells receiving VES treatments alone, implying that these changes are correlated with VES treatments but are not causal for apoptosis. However, treatments with VES + RRR-alpha-tocopherol decreased AP-1 binding to consensus DNA oligomer, suggesting AP-1 involvement in apoptosis induced by VES treatments.
 ...
PMID:RRR-alpha-tocopheryl succinate inhibits EL4 thymic lymphoma cell growth by inducing apoptosis and DNA synthesis arrest. 897 Jan 89

Human malignant melanoma is notoriously resistant to pharmacological modulation. We describe here for the first time that the synthetic retinoid CD437 has a strong dose-dependent antiproliferative effect on human melanoma cells (IC50: 5 x 10(-6) M) via the induction of programmed cell death, as judged by analysis of cell morphology, electron microscopical features, and DNA fragmentation. Programmed cell death was preceded by a strong activation of the AP-1 complex in CD437-treated cells as demonstrated by gel retardation and chloramphenicol transferase (CAT) assays. Northern blot analysis showed a time-dependent increase in the expression of c-fos and c-jun encoding components of AP-1, whereas bcl-2 and p53 mRNA levels remained constant. CD437 also exhibited a strong growth inhibitory effect on MeWo melanoma cells in a xenograft model. In tissue sections of CD437-treated MeWo tumors from these animals, apoptotic melanoma cells and c-fos overexpressing cells were colocalized by TdT-mediated deoxyuridine triphosphate-digoxigenin nick end labeling (TUNEL) staining and in situ hybridization. Taken together, this report identifies CD437 as a retinoid that activates and upregulates the transcription factor AP-1, leading eventually to programmed cell death of exposed human melanoma cells in vitro and in vivo. Further studies are needed to evaluate whether synthetic retinoids such as CD437 represent a new class of retinoids, which may open up new ways to a more effective therapy of malignant melanoma.
 ...
PMID:Treatment of melanoma cells with the synthetic retinoid CD437 induces apoptosis via activation of AP-1 in vitro, and causes growth inhibition in xenografts in vivo. 899 Oct 99

In the Syrian hamster, neonatal diethylstilbestrol (DES) treatment and then postpubertal estrogen stimulation induces hyperplasia plus apoptosis (preneoplastic responses) and ultimately neoplasia in the endometrial epithelial cell compartment. As part of a project to investigate the molecular and cellular mechanisms responsible for this phenomenon, expression of several proto-oncogenes (c-jun, c-fos, c-myc, bax, bcl-2 and bcl-x) was compared in estrogen-stimulated uteri from control versus neonatally DES-treated hamsters. According to Northern blot analysis of total uterine RNA, levels of the 3.2-kb c-jun and 2.4-kb c-myc transcripts were not altered by neonatal DES treatment. However, the 1.0 kb bax and 2.7 kb bcl-x transcript levels were significantly increased in the neonatally DES-exposed uteri. According to immunohistochemical analysis of paraformaldehyde-fixed and paraffin-embedded tissue sections, levels of c-Jun, c-Fos, c-Myc, Bax, and Bcl-x proteins were enhanced dramatically in both the luminal and glandular epithelial cells of neonatally DES-exposed uteri. In contrast, the immunostaining signal for Bcl-2 protein was decreased consistently in the epithelial cells of neonatally DES-exposed uteri. In conclusion, neonatal DES treatment induced persistent and epithelial cell-specific imbalances in the estrogen-regulated uterine expression of c-jun, c-fos, c-myc, bax, bcl-2, and bcl-x proto-oncogenes. These imbalances likely play a role in the molecular mechanism by which neonatal DES treatment induces altered estrogen responsiveness including hyperplasia, apoptosis, and ultimately neoplasia in the epithelial compartment of the hamster uterus.
 ...
PMID:Neonatal diethylstilbestrol treatment alters the estrogen-regulated expression of both cell proliferation and apoptosis-related proto-oncogenes (c-jun, c-fos, c-myc, bax, bcl-2, and bcl-x) in the hamster uterus. 910 Oct 88

Prognostic factors in oligodendrogliomas are not well defined, even considering the labeling index of proliferation markers. As in other neuroepithelial tumors, the difficulty in calculating cell loss may contribute to this uncertainty. Proliferation markers Ki-67/MIB.1 and PCNA, mitoses, apoptotic nuclei, p53 and bcl-2 expression were investigated in 98 oligodendrogliomas. Apoptosis was assessed by the aspect of nuclei, by in situ end-labeling (ISEL) technique and by c-Jun immunohistochemical demonstration. The Bcl-2 also was immunohistochemically studied for its anti-apoptotic role. Mitotic index (MI), labeling index (LI) for MIB.1 and PCNA and apoptotic index (AI) were calculated and compared among themselves and with histology and survival. It was found that AI correlated with MI (p = 0.001) and was significantly higher in anaplastic than in classic oligodendrogliomas (p = 0.001). Apoptosis occurred only slightly more frequently in cases with high LIs for proliferation markers (MIB.1 and PCNA) (p = non-significant) and it was definitely higher in p53-positive cases (p = 0.008). It did not correlate with bcl-2 which was poorly expressed in oligodendrogliomas, with the exception of cells with astrocytic features. Apoptotic index correlated very weakly with survival (p = 0.05); therefore, it cannot be considered a highly reliable prognostic factor in oligodendrogliomas.
 ...
PMID:Role of apoptosis in the prognosis of oligodendrogliomas. 922 Apr 57

The antimetabolite cytosine arabinoside (ara-C) represents a prototype of the nucleoside analog class of antineoplastic agents and remains one of the most effective drugs used in the treatment of acute leukemia as well as other hematopoietic malignancies. The ability of ara-C to kill neoplastic cells is regulated at three distinct but interrelated levels. First, the activity of ara-C depends on conversion to its lethal triphosphate derivative, ara-CTP, a process that is influenced by multiple factors, including nucleoside transport, phosphorylation, deamination, and levels of competing metabolites, particularly dCTP. Second, the antiproliferative and lethal effects of ara-C are linked to the ability of ara-CTP to interfere with one or more DNA polymerases as well as the degree to which it is incorporated into elongating DNA strands, leading to DNA fragmentation and chain termination. Finally, the fate of the cell is ultimately determined by whether a threshold level of ara-C-mediated DNA damage is exceeded, thereby inducing apoptosis, or programmed cell death. The latter process is influenced by components of various signal transduction pathways (e.g., PKC) and expression of oncogenes (e.g., bcl-2, c-Jun), perturbations in which may significantly alter ara-C sensitivity. A better understanding of these factors could eventually lead to the development of novel therapeutic strategies capable of overcoming ara-C resistance and improving therapeutic efficacy.
 ...
PMID:Ara-C: cellular and molecular pharmacology. 933 77

In previous reports we demonstrated that glucose deprivation induces metabolic oxidative stress in drug-resistant human breast carcinoma MCF-7/ADR cells (Lee, Y. J., Galoforo, S. S., Berns, c. M., Chen, J. C., Davis, B. H., Swim, J. E., Corry, P. M., and Spitz, D. R. (1998) J. Biol. Chem. 273, 5294-5299). In the study described here, we investigated intracellular responses to metabolic oxidative stress. Northern blots show an increase in the level of HSP70 and HSP28 mRNA in cells exposed to glucose-free medium for 1 h. One- and two-dimensional polyacrylamide gel analyses confirmed that glucose deprivation induced a family of HSPs, particularly an inducible HSP70. Overexpression of bcl-2 suppressed glucose deprivation-induced HSP70 gene expression, heat shock transcription factor-heat shock element binding activity, as well as c-Jun NH2-terminal kinase (JNK1) activation. Expression of a dominant-negative mutant of JNK1 also suppressed glucose deprivation-induced JNK1 activation as well as HSP70 gene expression. Taken together, the stress-activated protein kinase signal transduction pathway is involved in glucose deprivation-induced heat shock gene expression.
 ...
PMID:Metabolic oxidative stress-induced HSP70 gene expression is mediated through SAPK pathway. Role of Bcl-2 and c-Jun NH2-terminal kinase. 979 2

Bufalin, a component of the Chinese medicine chan'su, induces apoptosis in various lines of human tumor cells, such as leukemia HL60 and U937 cells, by altering the expression of apoptosis-related genes, for example, bcl-2 and c-myc. In this study, we characterized a gene that is involved in bufalin-induced apoptosis by the differential display (DD) technique. The partial nucleotide sequence of one of the differentially expressed clones obtained after treatment with bufalin was identical to that of the human gene for Tiam1. When U937 cells were treated with 10(-7) M bufalin, expression of both Tiam1 mRNA and the protein was induced 1 h after the start of the treatment. The increase of Tiam1 mRNA was transient but the level of Tiam1 protein continued to increase at least for 6 h. In addition, the activities of Rac1 and p21-activated kinase (PAK) were also stimulated by bufalin treatment. To evaluate the role of Tiam1 in the apoptotic process, we examined the effects of the expression of sense and antisense RNA for Tiam1 in U937 cells. Apoptosis was strongly induced by bufalin in cells that expressed sense RNA for Tiam1 as compared to apoptosis in control cells treated with bufalin only. Cells expressing antisense RNA for Tiaml were significantly more resistant than the control bufalin-treated cells to induction of DNA fragmentation in response to bufalin. Moreover, sense transformants had elevated activities of PAK and c-Jun NH2-terminal kinase (JNK). These results suggest that Tiaml might play a critical role in bufalin-induced apoptosis through the activation of Rac1, PAK, and JNK pathway.
 ...
PMID:Tiam1 is involved in the regulation of bufalin-induced apoptosis in human leukemia cells. 1022 92


1 2 3 4 5 Next >>