• 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.

• BMB Reports
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• v.38 no.4
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• pp.474-480
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• 2005

Curcumin, a major active component of turmeric, has been identified as an inhibitor of the transcriptional activity of activator protein-1 (AP-1). Recently, it was also found that curcumin and synthetic curcumin derivatives can inhibit the binding of Jun-Fos, which are the members of the AP-1 family, to DNA. However, the mechanism of this inhibition by curcumin and its derivatives was not disclosed. Since the binding of Jun-Fos dimer to DNA can be modulated by redox control involving conserved cysteine residues, we studied whether curcumin and its derivatives inhibit Jun-Fos DNA binding activity via these residues. However, the inhibitory mechanism of curcumin and its derivatives, unlike that of other Jun-Fos inhibitors, was found to be independent of these conserved cysteine residues. In addition, we investigated whether curcumin derivatives can inhibit AP-1 transcriptional activity in vivo using a luciferase assay. We found that, among the curcumin derivatives examined, only inhibitors shown to inhibit the binding of Jun-Fos to DNA by Electrophoretic Mobility Shift Assay (EMSA) inhibited AP-1 transcriptional activity in vivo. Moreover, RT-PCR revealed that curcumin derivatives, like curcumin, downregulated c-jun mRNA in JB6 cells. These results suggest that the suppression of the formation of DNA-Jun-Fos complex is the main cause of reduced AP-1 transcriptional activity by curcuminoids, and that EMSA is a suitable tool for identifying inhibitors of transcriptional activation.

• BMB Reports
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• v.47 no.8
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• pp.451-456
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• 2014

Parthenolide, a natural product derived from Feverfew, prevents septic shock and inflammation. We aimed to identify the effects of parthenolide on the RANKL (receptor activator of $NF-{\kappa}B$ ligand)-induced differentiation and bone resorbing activity of osteoclasts. In this study, parthenolide dose-dependently inhibited RANKL-mediated osteoclast differentiation in BMMs, without any evidence of cytotoxicity and the phosphorylation of p38, ERK, and $I{\kappa}B$, as well as $I{\kappa}B$ degradation by RANKL treatment. Parthenolide suppressed the expression of NFATc1, OSCAR, TRAP, DC-STAMP, and cathepsin K in RANKL-treated BMMs. Furthermore, parthenolide down-regulated the stability of c-Fos protein, but could not suppress the expression of c-Fos. Overexpression of NFATc1 and c-Fos in BMMs reversed the inhibitory effect of parthenolide on RANKL-mediated osteoclast differentiation. Parthenolide also inhibited the bone resorbing activity of mature osteoclasts. Parthenolide inhibits the differentiation and bone-resolving activity of osteoclast by RANKL, suggesting its potential therapeutic value for bone destructive disorders associated with osteoclast-mediated bone resorption.

• Asian-Australasian Journal of Animal Sciences
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• v.18 no.7
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• pp.1011-1016
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• 2005

In this study, 90 crossbred weaned pigs（Duroc${\times}$Landrace${\times}$Large White）weighing - 7.86${\pm}$0.06 kg each were randomly allotted to one of three dietary treatments. Control pigs were a fed corn-soybean meal diet with no additives. The two treatment groups were fed the basal diet supplemented either with 75 mg/kg Aureomycin or 0.4% fructooligosaccharides (FOS) in order to study the effects on performance, serological indices, and enteric morphology in addition to examining the content of volatile fatty acids in intestinal digesta. The results indicate that the diets containing FOS and antibiotics had a significant effect on feed conversion ratios (FCR) and diarrhea incidence, as well as increasing the concentrations of isobutyric and butyric acid and total VFAs in the caecum, and acetic acid, isovaleric acid, and total VFAs in feces. Supplementation with FOS also resulted in significantly longer mucosal villi height and a higher percentage of goblet cells compared with the control. No difference was found in crypt depth among the three treatments. While serum glucose levels were significantly higher following FOS supplement, differences in serum total protein, albumin, globulin, and urea nitrogen levels were not significant.

• Archives of Pharmacal Research
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• v.26 no.1
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• pp.53-57
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• 2003

We have found that ginsenoside Rc and Re induce c-fos in MCF-7 human breast carcinoma cells at both the mRNA and protein levels. However, neither ginsenoside activated the expression of reporter gene under the control of AP-1/TPA response elements. We have also examined the possibility that ginsenoside Rc and Re act by binding to intracellular steroid hormone receptors that act as transcriptional factors in the nucleus in inducing c-fos mRNA in MCF7 human breast carcinoma cells. However, ginsenoside Rc and Re did not bind to glucocorticoid, androgen, estrogen, or retinoic acid receptors as examined by the transcription activation of the luciferase reporter genes in CV-1 cells that were transiently transfected with the corresponding steroid hormone receptors and hormone responsive luciferase reporter plasmids. These data demonstrate that ginsenoside Rc and Re act via other transcription factors and not via estrogen receptor in c-Fos expression.

• Journal of Life Science
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• v.12 no.3
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• pp.317-324
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• 2002

We investigated the compositional changes of glycoconjugates (GCs) and expression of estrogen receptor (ER)-$\alpha$, c-fos and c-jun in the vagina of normal and ovariectomized rats by histochemical and immunohistochemical methods. The mucinous transformation of the superficial layer that occurred from late diestrus to proestrus was accompanied with extensive enrichment of GCs. According to the cyclic changes of the vagina, distinct reactivity patterns such as SBA affinity in the diestrus and Con A affinity in the diestrus and estrus phase was observed. However, weak staining for GCs was detected in the atrophied vaginal epithelium of ovariectomized rats. ER-$\alpha$ immunoreaction was mainly demonstrated in the basal layer of epithelium and estrus cycle-related variation in the number of ER-$\alpha$ immunoreaction were not pronounced. But the stromal cells showing ER-$\alpha$ immunoreaction were abundantly observed from diestrus to estrus phase. The most numerous c-fos immunoreactive cells were observed in the basal and intermediate layer of epithelium and stromal fells from the proestrus to estrus phase and c-jun in the basal layer of epithelium during estrus phase. The c-jun immunoreaction of stromal cells expressed only in the estrus phase. In the ovariectomized rats, a few of ER-$\alpha$, c-fos and c-jun immunoreactive cells were observed in the vaginal epithelium and no immunoreaction were found in the stromal cells. ER-$\alpha$ and c-fos immunoreaction fully expressed in the proestrus coincident with the cell proliferation, mutinous transformation and cornification of vaginal epithelium. These data indicate that vagina epithelium and stromal reals express multiple protein such as ER-$\alpha$, c-fos and c-iun by estrogen that may function in process of cells proliferation and differentiation of vagina epithelium.

• Korean Journal of Biological Psychiatry
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• v.20 no.4
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• pp.159-165
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• 2013

Objectives Mechanisms of clinical synergistic effects, induced by co-treatments of lithium and valproate, are unclear. Extracellular signal-regulated kinase (ERK) has been suggested to play important roles in mechanisms of the action of mood stabilizers. In this study, effects of co-treatments of lithium and valproate on the ERK1/2 signal pathway and its down-stream transcription factors, ELK1 and C-FOS, were investigated in vitro. Methods PC12 cells, human pheochromocytoma cells, were treated with lithium chloride (30 mM), valproate (1 mM) or lithium chloride + valproate. The phosphorylation of ERK1/2 was analyzed with immunoblot analysis. Transcriptional activities of ELK1 and C-FOS were analyzed with reporter gene assay. Results Single treatment of lithium and valproate increased the phosphorylation of ERK and transcriptional activities of ELK1 and C-FOS, respectively. Combined treatments of lithium and valproate induced more robust increase in the phosphorylation of ERK1/2 and transcriptional activities of ELK1 and C-FOS, compared to those in response to single treatment of lithium or valproate. Conclusions Co-treatments of lithium and valproate induced synergistic increase in the phosphorylation of ERK1/2 and transcriptional activities of its down-stream transcription factors, ELK1 and C-FOS, compared to effects of single treatment. The findings might suggest potentiating effects of lithium and valproate augmentation treatment strategy.

• Bulletin of the Korean Chemical Society
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• v.25 no.12
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• pp.1769-1774
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• 2004

Jun/Fos, a crucial factor in transmitting the tumor-promoting signal from the extracellular environment to the nuclear transcription machinery, has a dimerization interface possessing several coiled structural properties. Jun and Fos can interact with the DNA regulatory region, AP-1 (Activator Protein-1), which is composed of 5'-TGAC/GTCA-3'.$^1$ Curcumin is a well-known anticancer and anti-inflammatory compound.$^{2,3}$ It also acts as an inhibitor of the Jun-Fos function. c-Fos and c-Jun with a bZIP region are overexpressed in BL21 E. coli and purified with an $Ni^{2+}$ affinity column. The inhibitors of Fos-Jun-AP-1 complex formation were searched through the EMSA (electrophoresis mobility shift assay) experiment, and new curcuminoids were synthesized and investigated as to their inhibitory effect on the same system. Two curcuminoids showed a stronger inhibitory effect than curcumin. This inhibitory activity was quantified with EMSA. 1,7-bis(4-methyl)-1,6-heptadiene-3,5-dione (BJC003) and 1,7-bis(4-hydroxy-5-methoxy-3-nitrophenyl)-1,6-heptadiene-3,5-dione (BJC005) showed remarkably high inhibitory activities. $IC_{50}$ of 1,7-bis(4-methyl)-1,6-heptadiene-3,5-dione (BJC003) and 1,7-bis(4-hydroxy-5-methoxy-3-nitrophenyl)-1,6-heptadiene-3,5-dione (BJC005) are 8.98 ${\mu}M$ and 5.40 ${\mu}M$, respectively. However, 1,7-bis(4-methyl-3-nitrophenyl)-1,6-heptadiene-3,5-dione (BJC004) did not show inhibitory activity.

• Journal of Physiology & Pathology in Korean Medicine
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• v.22 no.5
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• pp.1299-1303
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• 2008

Since exercise training induces mechanical stress to the heart, we examined the activation pattern of mitogen-activated protein kinase(MAPK)s signaling pathway by immunohistochemistry. The immunoreactions of MAPKs signaling with c-fos and Schiff's reaction were increased in the cardiac muscle of exercised rat compared to normal one except immunoreaction for MEK1/2 and ERK1/2 and p38. However, the immunoreaction of phospho-JNK and phospho-p38 with early gene c-fos were arrested markedly in water extract of Alliium sativum (WEAS) treated rat compared to exercised one. Since MAPKs signaling does play a protective role in response to pathological stimulus in the heart, results in the present study suggest that WEAS may act as a alleviating agent for exercise-induced stress to. heart through regulating MAPKs signaling activation.

• Proceedings of the Korean Society of Applied Pharmacology
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• 1996.04a
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• pp.180-180
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• 1996

Previous studies have shown that kainic acid (KA) causes an elevation of hippocampal proenkephalin mRNA level. However, the role of proto-oncogene products, such as c-Fos, c-Jun and Fra proteins in the regulation of KA-induced proenkephalin mRNA increase in the hippocampus has not been well characterized. Thus, in the present study, the effect of cycloheximide (CHX) on KA-induced proenkephalin mRNA and immediate early gene products induction was examined. After pretreating with either vehicle or CHX (20 mg/kg, s.c.) for 30 min, KA (10 mg/kg) was administered s.c. The animals were sacrificed 1,2, or 8 hrs after KA administration. Total RNA and were isolated for Northern blot assay, and proteins were isolated for Western and electrophoretic gel-shift assays. First, we found that CHX inhibited KA-induced proenkephalin mRNA increase without altering intracellular proenkephalin protein level. Secondly, Western blot assays showed that KA increased c-Fos, c-Jun and Fra proteins at 1,2, and 8 hrs and CHX inhibited these immediate early gene products. Finally, electrophoretic gel shift assays revealed that KA increased both AP-1 and ENKCRE-2 DNA binding activities. Furthermore, CHX attenuated KA-induced AP-1 and ENKCRE-2 DNA binding activities. Both AP-1 and ENKCRE-2 DNA binding activities were abolished by cold AP-1 or ENKCRE-2 oligonucleotides, and further reduced by antibodies against c-Fos or c-Jun. Antibody against CREB reduced ENKCRE-2, but not AP-1, DNA binding activity. Our results suggest that on-going protein synthesis is required for elevation of hippocampal proenkephalin mRNA level induced by KA. All c-Fos, c-Jun, and Fra proteins appears to be involved in the regulation of hippocampal proenkephalin mRNA level induced by KA (This study was supported by a grant from KOSEF).