• YAKHAK HOEJI
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• v.41 no.1
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• pp.81-85
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• 1997

Ceramide has been suggested as an important mediator of the effects of extracellular agonists on cell growth inhibition, differentiation, apoptosis. However the biochemical sign aling mechanism involved in transducing the effects of ceramide on leukemia cell differentiation is still unclear. In these respects, we examined the regulatory effects of ceramide on c-jun gene expression during differentiation. In U-937 cells. ceramide increased c-jun mRNA levels in a time-dependent manner. The half life, of c-jun mRNA was 30 min. In contrast, inhibition of protein synthesis with cycloheximide in the absence, of transcription with actinomycin D increased the half-life of c-jun mRNA in ceramide-treated U-937 cells to more than 90 min. In order to examine whether ceramide-inhibited c-jun gene expression is regulated through ceramide-activated protein phosphatase (CAPP), a direct target for the action of ceramide, okadaic acid were treated to the cells. Okadaic acid inhibited enhancement of c-jun mRNA induced by C2-ceramide in a dose-dependent manner. These results suggested that ceramide increases c-jun mRNA level during differentiation in U-937 cells and regulates the gene expression on posttranscriptional level. In addition, we provide the evidence that CAPP is involved in ceramide-induced c-jun gene expression in U-937 cells.

• Molecules and Cells
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• v.24 no.2
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• pp.210-214
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• 2007

The 90-kDa heat shock protein (HSP90) normally functions as a molecular chaperone participating in folding and stabilizing newly synthesized proteins, and refolding denatured proteins. The HSP90 inhibitor geldanamycin (GA) occupies the ATP/ADP binding pocket of HSP90 so inhibits its chaperone activity and causes subsequent degradation of HSP90 client proteins by proteasomes. Here we show that GA reduces the level of endogenous c-Jun in human embryonic kidney 293 (HEK293) cells in a time and dose dependent manner, and that this decrease can be reversed by transfection of HSP90 plasmids. Transfection of HSP90 plasmids in the absence of GA increases the level of endogenous c-Jun protein, but has no obvious affect on c-Jun mRNA levels. We also showed that HSP90 prolongs the half-life of c-Jun by stabilizing the protein; the proteasome inhibitor N-benzoyloxycarbonyl (Z)-Leu-Leu-leucinal (MG132) blocks the degradation of c-Jun promoted by GA. Transfection of HSP90 plasmids did not obviously alter phosphorylation of c-Jun, and a Jun-2 luciferase activity assay indicated that over-expression of HSP90 elevated the total protein activity of c-Jun in HEK293 cells. All our evidence indicates that HSP90 stabilizes c-Jun protein, and so increases the total activity of c-Jun in HEK293 cells.

• Proceedings of the Korean Fiber Society Conference
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• 1986.06a
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• pp.46-46
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• 1986

• BMB Reports
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• v.43 no.1
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• pp.57-61
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• 2010

Activator protein-1 can induce either cell survival or death, which is controlled by opposing effects of different Jun members. It is generally accepted that c-Jun is pro-apoptotic, but that JunD is anti-apoptotic in stress-exposed cells. Additionally, although there are reports suggesting that JunB plays a protective role, its role in stress-induced apoptosis remains unclear. Here, we investigated the role of JunB in $H_2O_2$-induced cell death using cells that over-expressed the protein or were transfected with si-JunB. Inhibition of JunB expression accelerated $H_2O_2$-mediated loss of mitochondrial membrane potential (MMP) and cytotoxicity. Conversely, over-expression of JunB protein led to significant inhibition of the MMP loss and cell death. The increase in JunB expression also attenuated nuclear relocation of apoptosis-inducing factor and mitochondrial Bcl-2 reduction that occurred following $H_2O_2$ exposure. These results suggest that JunB can signal survival against oxidant-mediated cell death by suppressing mitochondrial stress.

• Clinical and Experimental Reproductive Medicine
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• v.26 no.2
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• pp.149-156
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• 1999

Steroid hormone is known to cause the dynamic changes of mammalian uterus during reproductive cycle, which are modulated via hypothalamus-pituitary -gonad reproductive endocrine axis. Although there were so many studies about estrogenic regulation of uterine growth and differentiation. There is little information about the effect of estrogen on the expression of various transcription factors involved in gene expression. Thus the present study was designed to demonstrate E induced expression of c-fos, c-jun, hsp25 mRNA in rat uterus. Employing Northern blot analysis, we studied the temporal expressions of c-fos, c-jun, and hsp25 messenger RNAs (mRNAs) elicited by a single 17beta-estradiol (E) treatment in the uteri of bilaterally ovariectomized adult rats. c-fos, c-jun, and hsp25 mRNA levels were increased and peaked at 3h after E administration, and then c-fos and c-jun mRNA levels were rapidly decreased to basal control level while, increased hsp25 mRNA levels were sustained till 12h post E treatment. To test the estrogenic effect on the increase of c-fos, c-jun, and hsp25 mRNA levels, we also examined the effects of antiestrogen (tamoxifen). Pretreatment with tamoxifen effectively blocked the E-induced increase of c-fos, c-jun, and hsp25 mRNA levels at 3h post E treatment. Present results suggest that transient increase of c-fos and c-jun protooncogene mRNA at the early time and simultaneous expression of hsp25 mRNA contribute to the response of uterine tissues to E in adult female rats.

• Herbal Formula Science
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• v.10 no.1
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• pp.73-80
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• 2002

We have examined the purgative effect of three Jechun-jun formulas in sprague dawley(SD) rat. Three jechun-jun formulas were Jechun-jun(Sample I ) and augmented Jechun-jun(Sample II) and augmented Jechun-jun add rhubarb(sample III ). We examined the amount and the humidity of feces in rat. The experimental animals were devided into four groups. as control group and three Jechun-jun (sample I, II, III). We administerd the water extract of sample I, II, III to rat per oral for 8days long. After every 24hours measured the amount of wet feces from rats in metabolic cage. Humidity rate of feces from rat was at first measure wet feces for 24hours (W) and measure dried feces (W1) and then we consider W-W1 as humidity. High humidity rate means constipation changes into moistening stool. The amount of wet feces and humidity rate of feces in rats were increased in sample I, II, III. Sample I has highest humidity rate of feces. so showed strong moistening effect. Sample II has mild effect in treating constipation. sample III has most amount of wet feces. in conclusion Jechun-jun has an effect of moistening stool. and augmented Jechun-jun add rhubarb has strong purgative effect.

• Biomolecules & Therapeutics
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• v.29 no.2
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• pp.195-204
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• 2021

Cereblon (CRBN), a substrate receptor of cullin 4-RING E3 ligase (CRL4) regulates the ubiquitination and degradation of c-Jun, mediating the lipopolysaccharide-induced cellular response. However, the upstream signaling pathway that regulates this process is unknown. In this study, we describe how endoplasmic reticulum (ER) stress reversely regulates sequestosome-1 (p62)and c-Jun protein levels. Furthermore, our study reveals that expression of p62 attenuates c-Jun protein levels through the ubiquitinproteasome system. Conversely, siRNA knockdown of p62 elevates c-Jun protein levels. Immunoprecipitation and immunoblotting experiments demonstrate that p62 interacts with c-Jun and CRBN to form a ternary protein complex. Moreover, we find that CRBN knockdown completely abolishes the inhibitory effect of p62 on c-Jun. Using brefeldin A as an inducer of ER stress, we demonstrate that the p62/c-Jun axis participates in the regulation of ER stress-induced apoptosis, and that CRBN is required for this regulation. In summary, we have identified an upstream signaling pathway, which regulates p62-mediated c-Jun degradation. Our findings elucidate the underlying molecular mechanism by which p62/c-Jun axis regulates the ER stress-induced apoptosis, and provide a new molecular connection between ER stress and apoptosis.

• Journal of Life Science
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• v.26 no.12
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• pp.1383-1391
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• 2016

Anti-estrogen drugs such as tamoxifen have been used for treating patients with ER-positive, early breast cancer. However, resistance to anti-estrogen treatment is inevitable in most patients. Breast cancer anti-estrogen resistance-3 (BCAR3) has been identified as the protein responsible for the induction of tamoxifen resistance in estrogen-dependent human breast cancer. We have previously reported that BCAR3 regulates the cell cycle progression and the signaling pathway of EGF and insulin leading to DNA synthesis. In this study, we investigated the functional role of BCAR3 in regulating c-Jun transcription in non-tumorigenic human breast epithelial MCF-12A cells. A transient transfection of BCAR3 increased both the mRNA and protein of c-Jun expression, and stable expression of BCAR3 increased c-Jun protein expression. The overexpression of BCAR3 directly activated the promoter of c-jun, AP-1, and SRE but not that of $NF-{\kappa}B$. Furthermore, single-cell microinjection of BCAR3 expression plasmid in the cell cycle-arrested MCF-12A cells induced c-Jun protein expression, and co-injection of dominant negative mutants of Ras, Rac, and Rho suppressed the transcriptional activity of c-Jun in the presence of BCAR3. Furthermore, stable expression of BCAR3 increased the proliferation of MCF-12A cells. The microinjection of inhibitory materials such as anti-BCAR3 antibody and siRNA BCAR3 inhibited EGF-induced c-Jun expression but did not affect IGF-1 induced upregulation of c-Jun. Taken together, we propose that BCAR3 plays a crucial role in c-Jun protein expression and cell proliferation and that small GTPases (e.g., Ras, Rac, and Rho) are required for the BCAR3-mediated activation of c-Jun expression.

• Journal of Physiology & Pathology in Korean Medicine
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• v.24 no.1
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• pp.143-151
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• 2010

In Vivo and In vitro antispasmodic effects of Jun-Si-Baek-Chul-San, a Traditional Korean Polyherbal Medicineconsisted of 7 types of herbs were observed in the present study. To clarify the effects of Jun-Si-Baek-Chul-San, on accelerating small intestinal movement induced by the stimulation of cholinergic neurotransmission, we evaluated the effects of Jun-Si-Baek-Chul-San on In vivo carbachol (an acetylcholinergic agent)-accelerated mice small intestinal transit and on In vitro contractions induced by low-frequency electrostimulation, KCl, histamine or acetylcholine using isolated guinea pig ileum. To induce the acceleration of mice small intestinal transit, Carbachol 1 mg/kg was once subcutaneously dosed 15min before last administration of the test drugs. In the present study, Jun-Si-Baek-Chul-San 500, 250 and 125 mg/kg or domperidone 20 mg/kg were orally pretreated on the carbachol-accelerated mice small intestinal transit once a day for 7 days and the small intestinal transit rateof activated charcoal powder were monitored. In vitro assays, Jun-Si-Baek-Chul-San1, 0.1, 0.01 and 0.001 mg/ml or domperidone $2{\times}10^{-5}M$ were treated 10min before ileal contraction was induced by filed stimulation, acetylcholine, KCl and histamine, and the % changes of contractions were observed compared to the treatment of inducer alone. In spontaneous contraction, the % changes of contractions were observed compared to treatment of vehicle alone at 10min after Jun-Si-Baek-Chul-San or domperidone treatment. The efficacy of Jun-Si-Baek-Chul-San was compared to those of domperidone. High concentration, 1 mg/ml of Jun-Si-Baek-Chul-San was found to decrease the spontaneous contraction of the isolated guinea-pig ileum. In addition, Jun-Si-Baek-Chul-San decrease contractions induced by electrostimulation, acetylcholine, histamine and KCl in the isolated guinea-pig ileum. In addition, Jun-Si-Baek-Chul-San effectively inhibited the accelerated small intestinal movement induced by carbachol stimulation of cholinergic neurotransmission in In vivo. Based on the results, although the exact molecular or action mechanism and which herbs or compound in Jun-Si-Baek-Chul-San are responsible for actions, it was concluded that Jun-Si-Baek-Chul-San normalization in the accelerated intestinal motility might be interfere with a variety of muscarinic, adrenergic and histaminic receptor activities or with the mobilization of calcium ions required for smooth muscle contraction non-specificly. Therefore, it is expected that Jun-Si-Baek-Chul-San will be promising as a prescription of clinical treatment of digestive tract disorders such as accelerated the motility of intestine, diarrhea or intestinal painful contractions.

• The Journal of the Korea Contents Association
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• v.11 no.1
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• pp.245-253
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• 2011

This study is to examine the effect of swimming exercise on the expression of c-fos, c-jun protein in rat hippocampus. 4-weeks aged rats and 16-weeks aged rats were used in experimental materials. All of two groups were classified into control and swimming exercise group. Swimming exercise was practiced for an hour a day. The results were got as follows after practical application in 1 day, 3days, 7 days. The expression of c-fos, c-jun protein was increased in all of the two experimental groups significantly in 1 day, 3days, 7 days. It was increased gradually in order of after 1 day, 3days, 7 days. There seems to be the effect of swimming exercise increasing the expression of c-fos, c-jun protein in hippocampus. Therefore swimming exercise can improve cognitive function such as learning and memory and prevent through activating immediate - early gene by swimming exercise. And it seems to have the positive effect on growth and recovery of nerve.