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At least 55 records · Page 3Linked to original sources
PubMed1995

Arachidonic acid induces c-jun gene expression in stromal cells stimulated by interleukin-1 and tumor necrosis factor-alpha: evidence for a tyrosine-kinase-dependent process.

We have previously shown that granulocyte-macrophage colony-stimulating factor (GM-CSF) gene expression induced by interleukin-1 (IL-1) and tumor necrosis factor-alpha (TNF-alpha) in the murine stromal cell line +/+.1-LDA 11 involves activation of phospholipase A2 (PLA2). Furthermore, induction of GM-CSF gene expression due to release of arachidonic acid as a result of PLA2 activation was mediated by the transcriptional factor c-jun. In the present study, we have investigated the potential mechanism involved in the induction of c-jun gene expression by arachidonic acid. Arachidonic acid induced transcription of c-jun mRNA. Downregulation of protein kinase C (PKC) by chronic exposure of stromal cells to the phorbol ester 12-O-tetradecanoyl-phorbol-13-acetate (TPA; 400 nmol/L) did not effect c-jun expression induced by arachidonate. Moreover, pretreatment of cells with the PKC inhibitor, calphostin C (1 mumol/L), caused a marked decrease of c-jun expression induced by TPA, but had no influence on c-jun expression induced by arachidonate. To explore the hypothesis that a tyrosine kinase signalling pathway, independent of PKC activation, was involved in arachidonate-induced c-jun expression, stromal cells were pretreated with the protein tyrosine kinase inhibitor, genistein, before challenge with arachidonic acid. Arachidonate 50 mumol/L)-induced c-jun expression was inhibited, in a dose- and time-dependent manner, by genistein. Genistein similarly inhibited c-jun expression in stromal cells exposed to IL-1 (500 U/mL) plus TNF-alpha (500 U/mL). The potential role of a tyrosine kinase pathway in arachidonate-mediated c-jun expression was further investigated by assaying the tyrosine kinase activity of cells challenged with arachidonic acid, IL-1, and TNF-alpha. Exposure of stromal cells to arachidonic acid induced a 2.1-fold increase in intracellular tyrosine kinase activity determined by phosphorylation of the synthetic peptide, raytide, in the presence of [gamma-32P]-ATP. Similarly, IL-1 and TNF-alpha induced 1.7- and 2.4-fold increases in tyrosine protein kinase activity, respectively. The effect of arachidonic acid on tyrosine kinase activity was inhibited by genistein and was enhanced by sodium vanadate. The increase of protein tyrosine kinase activity detected in arachidonate-stimulated cells was associated, in a dose- and time-dependent fashion, with tyrosine phosphorylation of 240-, 40-, and 29-kD substrates. These results are consistent with the hypothesis that a tyrosine phosphorylation process is triggered by arachidonate as an early event in the signalling pathway that leads to increased expression of c-jun.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗
PubMed1997

Regulation of c-jun gene expression in endothelial cells by the protein kinase inhibitor staurosporine.

The proto-oncogene c-jun, a member of the family of immediate-early genes, is transcriptionally induced in different cell types by a variety of stimuli, including mitogens, tumor promoters, growth factors. We show here that the protein kinase inhibitor staurosporine, which inhibits both the serine-threonine and tyrosine specific protein kinases, also causes differential regulation of the c-jun gene in endothelial cells. Increasing concentrations of staurosporine modulated the steady-state levels of c-jun mRNA in bovine aortic endothelial (BAE) cells in a multiphasic manner. The half-life of c-jun mRNA did not change significantly under these conditions, suggesting that the modulations in the mRNA levels were caused primarily by differential transcriptional activity of the gene. The expression of c-jun gene is believed to be regulated by its own product, the JUN protein, which constitutes a major component of the inducible transcription factor AP-1. In order to test whether the differential regulation of c-jun gene was caused by the differential activation (or inactivation) of the AP-1 transcription factor, the DNA-binding activity of this transcription factor in staurosporine-treated cells was measured. Gelshift analysis with a synthetic oligonucleotide probe showed modest effects of staurosporine on the DNA-binding activity of the transcription factor AP-1. The changes observed in the DNA-binding activity of AP-1 did not parallel the changes observed in the steady-state levels of c-jun mRNA. Similarly, the expression of an AP-1 dependent reporter gene construct was regulated in a fashion entirely different from the c-jun gene during the same protein kinase inhibitory conditions. These results suggest the existence of an alternative pathway that regulates the c-jun gene expression in endothelial cells independent of both the protein kinase and AP-1 transcription factor activation steps.

Animals↗
PubMed1995

Induction of c-fos and c-jun gene products and heat shock protein after brief and prolonged cerebral ischemia in gerbils.

BACKGROUND AND PURPOSE: Proto-oncogene activation and induction of heat shock protein (HSP) occur in response to various stimuli to brain, but the role in neuronal survival after cerebral ischemia remains uncertain. We compared the extent of insults and induction of c-fos and c-jun gene products (c-FOS and c-JUN) as well as HSP in ischemic and postischemic gerbil brains immunohistochemically. METHODS: Common carotid arteries of Mongolian gerbils were occluded for 5 or 15 minutes and recirculated for 0 minutes to 7 days. Antibodies for c-FOS, c-JUN, and HSP 70 were used for immunohistochemistry, and positive reactions were semiquantitatively analyzed. The presence of ischemic and postischemic lesions was ascertained with an antibody for microtubule-associated proteins. RESULTS: After ischemia for 15 minutes and reperfusion, c-FOS was induced promptly after 1 to 6 hours in pyramidal cells of the CA3 and CA4 regions, while c-JUN became visible in the same areas after recirculation for 4 to 48 hours. HSP 70 was detected after recirculation for 24 hours in the CA3 region. In layers I and II of the cerebral cortex, c-FOS and c-JUN peaked at 3 hours and HSP 70 at 96 hours. Induction of these proteins was absent or negligible in the areas that developed ischemic or postischemic lesions, including the subiculum-CA1 and CA1 regions of the hippocampus and layers III/IV and Vb/VI of the cerebral cortex. After shorter ischemia for 5 minutes and reperfusion, c-FOS and c-JUN were rapidly induced at 15 minutes to 1 hour except for the subiculum-CA1 and CA1 regions of the hippocampus. Induction of HSP 70 did not occur for 24 hours and was noted only in the hippocampus. CONCLUSIONS: Induction of c-FOS and c-JUN occurred in the areas surviving after transient cerebral ischemia, but the extent of induction and the latent period varied depending on the duration of the insult and the location. In the areas with ischemic or postischemic damage detected by loss of the reaction for microtubule-associated proteins, the induction of c-FOS and c-JUN was either absent or minimal, suggesting that active induction of those immediate early gene products occurred early in surviving neurons. On the other hand, the induction of HSP 70 did not occur until reperfusion for 24 hours and actively occurred only in the areas with earlier induction of c-FOS and/or c-JUN, suggesting that the induction of HSP 70 occurred in neurons that survived to that point, but it did not participate in early responses for neuronal survival after global cerebral ischemia.

Animals↗
PubMed1993

The induction of jun genes during the reversible changes induced with sodium butyrate on the differentiation of F9 cells.

Sodium butyrate (NaB) induces the phenotypic changes and differentiation markers in embryonal carcinoma F9 cells (Kosaka et al., Exp. Cell Res. 192, 46, 1991). However, the effects are rapid and reversible and different from those induced with retinoic acid (RA). We examined the expression of jun genes during differentiation induced with NaB and compared it with that of RA induction. Although c-jun expression was induced with RA, rapid and predominant induction of junB expression was specifically observed with NaB, which is regulated by both transcriptional and post-transcriptional mechanisms. These results suggest that the mechanism of differentiation induced with NaB differs from that of RA; the former may be mediated by the junB gene and the latter by c-jun.

Animals↗
PubMed1992

Interleukin-1 induces c-fos and c-jun gene expression in T helper type II cells through different signal transmission pathways.

Interleukin (IL)-1 induces proliferation and expression of several protooncogenes in the T helper 2 cell line D10A. We have analyzed the signal transmission pathways activated by IL-1 in these cells, leading to the expression of c-jun and c-fos. IL-1 induced c-jun gene transcription and mRNA expression by means of a pathway dependent on protein tyrosine kinase activity since tyrphostin, a specific inhibitor of tyrosine kinase, inhibited this induction. This mechanism of transmission signaling was independent of protein kinase C (PKC) and was linked to the 80-kDa IL-1 receptor (IL-1R). In addition, phorbol esters did not induce c-jun mRNA expression, whereas c-fos mRNA expression mediated by IL-1 dependent on PKC; this pathway was linked to a different, still unidentified IL-1R that was functional in the D10A cell line. Accumulation of intracellular cAMP generated by IL-1 through the 80-kDa IL-1R negatively regulated c-fos expression which was induced by IL-1 through PKC activation. We conclude that IL-1 modulates the expression of c-fos in D10A cells by occupying of two independent IL-1R that are linked to different signal transduction pathways.

Cyclic AMP↗
PubMed1994

1-beta-D-arabinofuranosylcytosine activates serine/threonine protein kinases and c-jun gene expression in phorbol ester-resistant myeloid leukemia cells.

1-beta-D-Arabinofuranosylcytosine (ara-C) is an effective antileukemic agent that misincorporates into DNA. Recent studies have demonstrated that ara-C treatment is associated with transient induction of the c-jun early response gene. The present studies have examined the effects of ara-C on c-jun expression in a phorbol ester-resistant variant of the HL-60 myeloid leukemia cell line, designated HL-525, that is deficient in protein kinase C (PKC)-mediated signal transduction and fails to respond to 12-O-tetradecanoylphorbol-13-acetate with induction of c-jun transcripts. The results demonstrate that treatment of HL-525 cells with ara-C is associated with transcriptional activation of the c-jun gene. We also demonstrate that ara-C treatment is associated with activation of a PKC-like activity. Partial purification of this Ca(2+)-independent activity has demonstrated phosphorylation of synthetic peptides derived from (a) amino acids 4-14 of myelin basic protein and (b) the pseudosubstrate region of PKC (amino acids 19-31), with substitution of Ala25 with serine. The finding that the ara-C-induced activity is inhibited by the pseudosubstrate PKC(19-36) supports the activation of a PKC-like enzyme. Because PKC can act upstream of the mitogen-activated protein (MAP) kinases, we studied the effects of ara-C treatment on MAP kinase activity. The results demonstrate that MAP kinase is activated in ara-C-treated cells and that the kinetics of this activation are similar to those of the PKC-like activity. Because 12-O-tetradecanoylphorbol-13-acetate has little, if any, effect on the PKC-like and MAP kinase activities in HL-525 cells, these findings suggest that ara-C activates a distinct signaling cascade that may contribute to induction of the c-jun gene.

Cytarabine↗
PubMed2002

The effects of vitamin E succinate on the expression of c-jun gene and protein in human gastric cancer SGC-7901 cells.

AIM: To investigate the effects of vitamin E succinate (VES) on the expression of c-jun gene and protein in human gastric cancer SGC-7901 cells. METHODS: After SGC-7901 cells were treated with VES at different doses (5,10,20 mg x L(-1)) at different time, reverse transcription-PCR technique was used to detect the level of c-jun mRNA; Western Blot was applied to measure the expression of c-jun protein. RESULTS: After the cells were treated with VES at 20 mg x L(-1) for 3 h, the expression rapidly reached its maximum that was 3.5 times of UT control (P<0.01). The level of c-jun mRNA was also increased following treatment of VES for 6 h. However,the expression after treatment of VES at 5 mg x L(-1) for 24 h was 1.6 times compared with UT control (P<0.01). Western blot analysis showed that the level of c-jun protein was obviously elevated in VES-treated SGC-7901 cells at 20 mg x L(-1) for 3 h. The expression of c-jun protein was gradually increased after treatment of VES at 20 mg x L(-1) for 3, 6, 12 and 24 h, respectively, with an evident time-effect relationship. CONCLUSION: The levels of c-jun mRNA and protein in VES-treated SGC-7901 cells were increased in a dose- and time-dependent manner; the expression of c-jun was prolonged by VES, indicating that c-jun is involved in VES-induced apoptosis in SGC-7901 cells.

Blotting, Western↗
PubMed1996

Temporal changes in insulin-like growth factor I, c-fos, and c-jun gene expression during hyperplastic kidney growth in weanling rats.

We have previously determined that compensatory renal growth (CRG) during the initial 24-48 h after uninephrectomy (UNX) is GH independent in weanling animals, but associated with significant increases in insulin-like growth factor I (IGF-I) and IGF-I receptor gene expression. The purpose of the present study was to determine the temporal sequence of molecular and cellular events that occur at various time points (1, 6, 12, 18, 24, 48, and 72 h post-UNX) during this early period of accelerated renal growth in the weanling (21- to 25-day-old) rat. Rapid and sustained increases in steady state renal IGF-I receptor and IGF-I messenger RNA (mRNA) were observed at 1 and 6 h, respectively, and remained elevated in the remnant kidneys until 72 h post-UNX. The mRNAs for the early response genes, c-fos and c-jun, were not induced in the remnant kidneys from weanling rats until between 12-18 h, but were also sustained through 48 h post-UNX. Increases in remnant kidney DNA content and [3H]thymidine incorporation also occurred from 18-48 h post-UNX and returned to baseline levels by 72 h post-UNX, indicating that the hyperplastic response in the weanling remnant kidney occurs over a discrete period early after UNX. Neither IGF-I nor early response genes were elevated in kidneys from adult animals, which exhibited only hypertrophic renal growth at those early time points after UNX. These findings suggest that early CRG in the weanling rat is associated with rapid increases in IGF-I mRNA followed by a rise in c-fos and c-jun gene expression and a mitogenic response. Furthermore, when the mRNA levels of IGF-I and early response genes returned to baseline levels, mitogenic growth stopped, and slower prolonged hypertrophic renal growth ensued.

Animals↗
PubMed1992

Gonadotropin induces expression of c-fos and c-jun genes in rat ovaries.

It has been shown that the expression of protooncogenes, c-fos and c-jun, induced by growth factors and hormones plays important roles in cellular proliferation, tissue differentiation and transcription of certain genes. Since gonadotropin stimulates ovarian steroidogenesis and cellular proliferation, we investigated whether gonadotropin affects the expression of c-fos and c-jun genes in rat ovaries. The expression of mRNA coding side chain cleavage enzyme (P450scc), the rate limiting enzyme in ovarian steroidogenesis was also studied. The effect of gonadotropin was examined in female rats whose gonadotrophs were medically ablated by GnRH agonist (TAP-144-SR). After intravenous administration of pregnant mare's serum gonadotropin (PMSG:30 IU/rat), their ovaries were dissected out at various time intervals and total RNA was extracted. Changes in the levels of c-fos, c-jun and P450scc mRNAs were determined by Northern blot analysis. The levels of c-fos and c-jun mRNAs increased rapidly and transiently with the peak levels at 15 min after PMSG administration. The levels of both mRNAs were decreased by 30 to 60 min. On the other hand, the levels of P450scc mRNA started to increase 60 min after PMSG. These results indicate that gonadotropin-induced increase in the expression of c-fos and c-jun genes may play important roles in mediating the action of gonadotropin on the ovaries.

Actins↗
PubMed2000

A short region containing an AP-1 binding site is essential for transforming growth factor-beta-induced c-jun gene expression in osteoblastic cells.

Transforming growth factor-beta (TGF-beta) is a multifunctional regulatory peptide that elicits different responses in different cell types. Much remains unknown about the pathway of intracellular TGF-beta signal transduction, but TGF-beta is known to induce expression of several genes by way of the transcription factor AP-1. We studied the mechanism that mediates TGF-beta-induced gene expression of c-jun, a component of AP-1, in MC3T3-E1 osteoblastic cells. To map in detail the corresponding responsive elements in the rat c-jun promoter, we generated a series of 5' deletion promoter/luciferase reporter gene constructs. Transient cell transfection assays identified the region located between positions -79 and -59 as being critical for the TGF-beta response and for the basal activity of the promoter. Gel mobility shift assays indicated specific binding of nuclear proteins to this 21-bp region of the c-jun promoter containing an AP-1 binding site. These results show that the AP-1-dependent mechanism is involved in TGF-beta-induced increase of c-jun induction, suggesting positive autoregulation of AP-1.

3T3 Cells↗
PubMed1998

Regulation of the c-jun gene in p210 BCR-ABL transformed cells corresponds with activity of JNK, the c-jun N-terminal kinase.

Activity of the c-jun N-terminal kinase (JNK) has been shown in hematopoietic cells transformed by p210 BCR-ABL. However, analysis has not been reported for hematopoietic cells on the consequences of this activity for c-jun promoter regulation within its distinctive proximal 8-base consensus CRE-like element, an element linked to JNK-mediated increase in c-jun transcription. In the present study, regulation of the proximal c-jun promoter was studied in murine myeloid cells transformed by p210 BCR-ABL. Promoter regulation in p210 BCR-ABL transformed cells was compared with regulation of the promoter in nontransformed interleukin-3 (IL-3)-dependent parental cells. The composition of nuclear AP-1 proteins contained within cells with p210 BCR-ABL, and their binding to the c-jun promoter proximal CRE-like element, was compared with the composition and binding of AP-1 proteins in IL-3-treated parental cells without p210 BCR-ABL. The present analysis found fivefold increased c-jun transcription occurring in p210 BCR-ABL transformed murine myeloid cells possessing a corresponding magnitude of increased kinase activity of JNK, compared with IL-3-stimulated parental cells. Augmented JNK activity was accompanied by increased nuclear abundance of c-jun and c-fos proteins that bound specifically to the proximal c-jun promoter CRE element. Also, representative human leukemic cell lines expressing p210 BCR-ABL and possessing abundant kinase activity of JNK, when compared with parental cells that were deficient in JNK activity, had increased c-jun and c-fos proteins. Finally, to show the relevance of these observations in model systems, we studied blast cells from patients with Philadelphia chromosome-positive acute leukemic transformation, and observed comparable activities of JNK catalysis and c-jun/AP-1 protein relative to the cell lines that possessed p210 BCR-ABL and JNK activity. These studies provide a basis for investigating the set of downstream genes which augmented c-jun/AP-1 activity enlists in the process of transformation by p210 BCR-ABL.

Animals↗
PubMed1997

Effects of the inhibition of p38/RK MAP kinase on induction of five fos and jun genes by diverse stimuli.

The ERK, JNK/SAPK and p38/RK MAP kinase subtypes are differentially activated by physiological, pharmacological and stress stimuli; all three subtypes are implicated in immediate-early (IE) gene induction by these agents. Here, we have asked whether inhibition of a single MAP kinase subtype under these conditions would generally alter induction of several IE genes in a similar way or whether this would differentially up- and down-regulate particular IE genes, an issue which bears on the question of whether individual MAP kinases are strictly targeted to specific IE genes, or whether they might catalyse phosphorylation events that affect several IE genes in the same way. SB 203580, an inhibitor of p38/RK, has been used to analyse the role of this kinase in the induction of five IE genes (c-fos, fosB, c-jun, junB and junD) under diverse conditions of stimulation. In C3H 10T1/2 cells, p38/RK and its downstream kinase MAPKAP K-2 are activated by all stimuli used with the exception of TPA. The specificity of SB 203580 as a p38/RK inhibitor in these cells is demonstrated; it does not affect ERKs or JNK/SAPKs but does result in a small increase in the activity of the upstream kinase MKK6, the principal p38/RK activator in these cells. We find that inhibition of p38/RK under these conditions produces general effects on all five IE genes as a group in three ways. First, induction of all five genes in response to okadaic acid or tumour necrosis factor-alpha (TNF-alpha) is not significantly altered by SB 203580. Second, in cells stimulated with anisomycin or U.V. radiation, SB 203580 potently inhibits all of the induced IE genes. Finally, SB 203580 enhances induction of all five IE genes in EGF-treated cells; these enhanced mRNA levels are not due to stabilisation of labile mRNA transcripts. The significance of these results to current thinking on the relationship between distinct MAP kinase subtypes and specific IE genes is discussed.

Animals↗
PubMed1998

Establishment of an apoptosis-resistant and growth-controllable cell line by transfecting with inducible antisense c-Jun gene.

F-MEL cells were transfected with the c-jun antisense gene located downstream of a glucocorticoid-inducible MMTV promoter, and the obtained cells were named c-jun AS cells. When the c-jun AS cells were treated with dexamethasone (DEX) in DMEM supplemented with 10% serum, the growth of the cells was completely suppressed for a duration of 16 days with a high cell viability exceeding 86%. The c-jun expression in the c-jun AS cells was suppressed moderately in the absence of DEX and strongly in the presence of DEX. The c-jun AS cells grew well and reached a density of 10(6) cells/mL without supplementation of any serum components. Viability was greater than 80% after the cells had been cultured for 8 days in the absence of DEX. The c-jun AS cells stayed at a constant cell density and high viability above 80% for 8 days when they were cultured in the presence of DEX under serum deprivation. In contrast, the wild type F-MEL cells were unable to grow and died by apoptosis in 3 days under serum deprivation. Internucleosomal cleavage of DNA, a landmark of apoptosis, was clearly detectable. Thus the c-jun AS cell line that is resistant to apoptosis induced by serum deprivation and can reversibly and viably be growth-arrested was established. A dual-signal model was proposed to explain the experimental result, the interlinked regulation of apoptosis, and growth by c-jun.

Animals↗
PubMed1990

Increased expression of c-jun gene during spontaneous hepatocarcinogenesis in LEC rats.

We have studied the expressions of nine proto-oncogenes (c-myc, N-myc, c-fos, C-jun, p53, H-ras, N-ras, c-raf, hst) and two other genes (PCNA, GST-P) during the spontaneous development of hepatocellular carcinomas (HCCs) in LEC rats. Expression of c-myc, H-ras, N-ras, C-raf, p53 and PCNA genes was detected, but this did not significantly change during the development of HCCs in LEC rats. Expression of N-myc and hst genes was not detectable. Expression of c-fos gene was detected in one HCC case out of four. Significantly increased expression of c-jun gene was observed in the liver tissues of LEC rats aged 8 months. This high expression was decreased with the development of HCCs. On the other hand, the expression of GST-P gene increased in parallel with the clinical course of the development of HCCs in LEC rats. The pattern of c-jun mRNA augmentation was different from that of GST-P mRNA. These observations suggest that c-jun gene may play a role in the spontaneous development of HCCs in LEC rats.

Age Factors↗
PubMed1996

Coordinate regulation of glucocorticoid receptor and c-jun gene expression is cell type-specific and exhibits differential hormonal sensitivity for down- and up-regulation.

We have previously proposed a novel mechanism for the coupled regulation of glucocorticoid receptor (GR) and c-jun transcription in triamcinolone acetonide (TA)-treated AtT-20 cells. This involved transcriptional interference of AP-1 (Fos/Jun)-driven gene transcription by the formation of inactive GR/Jun heterodimers. To further elucidate the molecular mechanism for GR autoregulation, the expression of GR and c-jun mRNA and protein levels were examined in both mouse L929 fibroblast cells and human CEM-C7 acute lymphoblastic leukemia cells. A rapid down-regulation of both GR and c-jun mRNA and protein levels occurs in TA-treated L929 cells. All-trans-retinoic acid (RA) treatment of Jun-deficient, mouse F9, teratocarcinoma cells causes the induction of c-jun expression. The increased expression of both c-jun mRNA and protein is accompanied by the induction of GR expression. These data further suggest that functional cJun is needed for the expression of the GR and c-jun genes in F9 cells. CEM-C7 cells undergo apoptosis after exposure to glucocorticoids. There is a parallel up-regulation of GR and c-jun mRNA levels in TA-treated CEM-C7 cells. This is accompanied by a concomitant increase in GR and cJun protein levels. Dose-response analyses reveal the expected coordinate regulation of both GR and c-jun mRNA and protein in L929 cells (decreasing) and in CEM-C7 cells (increasing). However, approximately 20-fold less TA is required for the inhibition of GR and c-jun expression as compared to that required for the stimulation of these two genes. These data demonstrate that the coordinate regulation of GR and c-jun gene expression is dose-dependent and cell type-specific. These results, along with previously reported data, suggest that GR complex formation with itself or with another transcription factor is important for the coordinate up- and down-regulation, respectively, of the GR and c-jun genes.

Animals↗
PubMed2003

[Effect of chlorimethylmercury on the expression of c-fos and c-jun genes in rat brain].

To study the role of immediate early genes (IEG) c-fos and c-jun in the neurotoxic mechanism of methylmercury chloride(MMC), expression of FOS and JUN in rat brains was observed by using immunohistochemical methods. In the test group MMC (5.0 mg/kg and 0.1 mg/kg) was injected into rats while in the control group normal saline was injected. The results showed that after rats exposed for 3 hours, the expression of FOS and JUN in brains was higher than those of the control rats, the results indicated that IEG could participate in the neurological toxicity induced by chlorimethylmercury.

Animals↗
PubMed1994

c-fos and jun gene expression in murine precursor B lymphocytes developed in the interleukin-7-dependent bone marrow cell culture.

We analyzed the expression of c-fos and jun family gene in murine pre-B cells developed in the interleukin-7-(IL-7) dependent bone marrow cell culture. The c-fos gene was expressed in the pre-B cells. The c-fos RNA became undetectable after IgM+ B cells were developed in the culture. The c-fos expression in the pre-B cells was IL-7-dependent. However, the c-fos RNA was not induced when the pre-B cells cultured without IL-7 for 6 h were restimulated with IL-7. The expression of c-jun RNA was slightly induced in the restimulated pre-B cells. The junB and junD RNA were the steady state level in the cells. These gene products formed AP-1 molecule in the pre-B cells. These results suggest that the AP-1 plays a role in the IL-7-dependent pre-B cell development.

Animals↗
PubMed2001

Dominant negative c-jun gene transfer inhibits vascular smooth muscle cell proliferation and neointimal hyperplasia in rats.

We previously reported that activator protein-1 (AP-1), containing c-Jun, is rapidly activated in balloon-injured artery. Therefore, we examined the role of c-Jun in vascular smooth muscle cell (SMC) proliferation, by using in vitro and in vivo gene transfer techniques. (1) Serum (2%) stimulation significantly increased AP-1 DNA binding activity in aortic SMCs, followed by the increase in both 3H-thymidine incorporation and cell number. Aortic SMCs were infected with recombinant adenovirus containing TAM67, a dominant negative c-Jun lacking transactivation domain of wild c-Jun (Ad-DN-c-Jun), to specifically inhibit AP-1. Ad-DN-c-Jun significantly inhibited serum-induced SMC proliferation, by inhibiting the entrance of SMC into S phase. (2) The effect of DN-c-Jun was examined on balloon injury-induced intimal hyperplasia in rats. Before balloon injury, DN-c-Jun was transfected into rat carotid artery using the hemagglutinating virus of Japan-liposome method. In vivo transfection of DN-c-Jun significantly inhibited vascular SMC proliferation in the intima and the media and subsequently prevented intimal thickening at 14 days after balloon injury. We obtained the first evidence that DN-c-Jun gene transfer prevented vascular SMC proliferation in vitro and in vivo, and c-Jun was involved in balloon injury-induced intimal hyperplasia. Thus, AP-1 seems to be the new therapeutic target for treatment of vascular diseases.

Animals↗