• Bulletin of the Korean Chemical Society
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• v.27 no.4
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• pp.535-538
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• 2006

In our previous studies, we have observed that curcumin and momordin I isolated from Ampelopsis radix inhibit the formation of Fos-Jun-activation protein-1 (AP-1) DNA complex. We have screened more effective compounds which have a 5-membered ring framework like momordin I and have modified disaccharide or carboxylic acid portions in momordin I. We synthesized momordin I derivatives according to the published method with slight modification. Synthetic momordin I derivatives showed remarkable inhibitory activities on Fos-Jun-AP-1 DNA complex formation results in in vitro assays. The $IC_{50}$ values of momordin I derivatives were about 4.0 $\mu$M in an electrophoretic mobility shift assay (EMSA). This value is about 125 times higher than that of curcumin and about 12 times higher than that for curcumin derivative C1, and moreover about 30 times higher than that for momordin I. We found momordin I derivatives (a) and (b) are the strongest inhibitory compound for Fos-Jun-AP-1 DNA complex formation.

• The Korean Journal of Physiology and Pharmacology
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• v.3 no.1
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• pp.69-74
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• 1999

Both direct and indirect environmental stress to brain were increase the expression of transcription factor c-fos in various populations of neurons. In this study, we examined whether the intraperitoneal injections of lidocaine at doses inducing convulsion within 10 min increased the level of c-fos mRNA and protein in forebrain areas. In situ hybridization using $[^{35}S]UTP-labeled$ antisense c-fos, cRNA increased c-fos mRNA levels though hippocampal formation, piriform cortex, septum, caudate-putamen, neostriatum, and amygdala within 2 hr. In parallel with the mRNA expression, c-FOS protein immunoreactivity was also observed in the same forebrain areas. In contrast to the seizure activity and widespread neuronal degeneration following a kainate treatment, injections of lidocaine did not produce neuronal death within 3 days. The present study indicates that lidocaine induces convulsion and c-fos expression without causing neurotoxicity.

• Bulletin of the Korean Chemical Society
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• v.20 no.8
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• pp.925-928
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• 1999

The process of transcription is the major point at which gene expression is regulated. The jun and fos families of eukaryotic transcription factor heterodimerize to form complexes capable of binding 5'-TGAGTCA-3'DNA elements (AP-1 binding site). To search for the inhibitors of the jun-fos-DNA complex formation, several natural products extracts were screened and methanol extract of tanshen (the dried roots of Salvia miltiorrhiza Bunge) showed remarkable inhibitory activity. The active compounds of the extracts were purified using re-peated column chromatography and recrystallization. Their structures were identified as tanshinone I and tanshinone IIA. Through the electrophoresis mobility shift assay and cell cytotoxicity test, tanshinone I and tanshinone IIA were identified as inhibitors that suppress not only AP-1 function but also the cell proliferation. Tanshinone I also suppressed the jun-fos-DNA complex formation in TPA-induced NIH 3T3 cells.

• Journal of Life Science
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• v.15 no.6 s.73
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• pp.928-934
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• 2005

ATF2 is a cellular transcription factor which belongs to the CREB/ATF class and it is leucine zipper protein which generally binds to DNA as dimers. This paper presents the procedure for subcloning the ATF2 gene and the results of experiment used the expressed ATF2. The pET expression vector was used since it produced 6xHis fusion protein for easy purification using affinity column. The Nickel chelating chromatography was used for Purifying the expressed ATE2 from E- codi BL2l. Subsequen시y In vitro binding pull-down assay showed the binding specificity of ATF2 with AP-1 family factors such as BATF, c-Fos, c-Jun and ATF2 itselgf. ATF2 forms homodimer as well as strong heterodimer with BATF. It also forms stable dimer with c-Jun but barely binds with c-Fos.

• Bulletin of the Korean Chemical Society
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• v.20 no.11
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• pp.1319-1322
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• 1999

Leucine zipper dynamically tunes the degree of bifurcation of the DNA binding segments in the basic region of the Fos-Jun bZIP complex. Molecular dynamics simulation indicated that site-specific mutagenesis of conserved leucine residues inside the leucine zipper domain caused the change of dynamic behavior of the basic region, and efficient DNA binding occurs only within a certain range of distance between the two DNA binding segments in the basic region. Distribution of α-helices in the hinge region is also suggested to influence the bifurcation of the DNA binding segments.

• 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).

• 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.25 no.9
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• pp.1043-1050
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• 2015

Glutamate is one of the principle transmitters in the CNS. Ionotropic receptors of glutamate, selectively activated by N-methyl-D-aspartate (NMDA), play an important role in the processes of cell development, learning, memory, and etc. On the other hand, many studies discovered that over-activation of glutamate receptors leads to neurodegeneration and are known to be implicated in major areas of brain pathology. Any sustained effect of a transient NMDA receptor activation is likely to involve signaling to the nucleus and to trigger coordinated changes in gene expression. Classically, a set of immediate-early genes are induced first; some of genes are by themselves transcription factors that control expression of other target genes. This study provides understanding of changes of inducible transcription factors mRNA levels with RT-PCR by inducing over-activation of NMDA receptor with intraperitoneal NMDA injection. The experimental conditions were varied by 1, 5, 25, and 125 g/ of body weight NMDA and measured transcription factors mRNA levels are Egr-1, c-Jun, JunB, and FosB. Based on result obtained, inducible transcription factors mRNA in NMDA injection to mice with 5 g/body weight showed the greatest change. And ITF mRNA showed greatest change 24 hr after injection. The expression level of JunB mRNA was markedly changed. Up to the present days, no study clearly understood how ITF mRNA affected the apoptosis of purkinje cells in the cerebellum. The current study improves the understanding of the mechanism of apoptosis of purkinje cells in the cerebellum.

• Archives of Pharmacal Research
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• v.27 no.8
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• pp.863-866
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• 2004

The effect of substance P (Sub P) injected intrathecally (I.t.) on c-fos mRNA expression in vari-ous tissues was examined in the present study. We found that a single administration of Sub P(0.5 nM) caused an increase of the c-fos mRNA level in the hypothalamic-pituitary-adrenal(HPA) axis, hippocampus, and spinal cord. The time-course study showed that c-fos mRNA level was maximal at 10 min and began to decrease 30 min after the Sub P injection in all tis-sues, and the Sub P-induced increase of the c-fos mRNA level was returned to the control level 1 h after the injection. The kinetics of the c-fos mRNA expression in mice that were repeatedly injected with Sub P (every 30 min interval up to 4 times) were different in the HPA axis, hippocampus, and spinal cord. The increased c-fos mRNA level in the hypothalamus and the spinal cord induced by I.t. injected Sub P remained at a high level. In the pituitary gland, adrenal gland, and hippocampus, the increased level of c-fos mRNA expression gradually returned to the control level during the repeated substance P injections up to 4 times. Our results suggest that spinally injected Sub P-induced pain stress increases c-fos mRNA expres-sion in the spinal cord, hippocampus, and HPA axis. In mice repeatedly injected with Sub P, the kinetics of c-fos mRNA appear to be different varied from tissue to tissue.

• Journal of Korean Neurosurgical Society
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• v.61 no.2
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• pp.186-193
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• 2018

Objective : The purpose of this study was to evaluate pain-related behaviors after bilateral C2 root resection and change in pain patterns in the suboccipital region in rats. Methods : Male Sprague-Dawley rats were randomly assigned to three groups (n=25/group); $n{\ddot{a}}ive$, sham, and C2 resection. Three, 7, 10, and 14 days after surgery, cold allodynia was assessed using $20{\mu}L$ of 99.7% acetone. c-Fos and c-Jun were immunohistochemically stained to evaluate activation of dorsal horn gray matter in C2 segments of the spinal cord 2 hours, 1 day, 7 days, and 14 days after surgery. Results : Three days after surgery, the response to acetone in the sham group was significantly greater than in the $n{\ddot{a}}ive$ group, and this significant difference between the $n{\ddot{a}}ive$ and sham groups was maintained throughout the experimental period (p<0.05 at 3, 7, 10, and 14 days). Seven, 10, and 14 days after surgery, the C2 root resection group exhibited a significantly greater response to acetone than the $n{\ddot{a}}ive$ group (p<0.05), and both the sham and C2 resection groups exhibited significantly greater responses to acetone compared with 3 days after surgery. No significant difference in cold allodynia was observed between the sham and C2 root resection groups throughout the experimental period. Two hours after surgery, both the sham and C2 root resection groups exhibited significant increases in c-Fos- and c-Jun-positive neurons compared with the naive group (p=0.0021 and p=0.0358 for the sham group, and p=0.0135 and p=0.014 for the C2 root resection group, respectively). One day after surgery, both the sham and C2 root resection groups exhibited significant decreases in c-Fos -positive neurons compared with two hours after surgery (p=0.0169 and p=0.0123, respectively), and these significant decreases in c-Fos immunoreactivity were maintained in both the sham and C2 root resection groups 7 and 14 days after surgery. The sham and C2 root resection groups presented a tendency toward a decrease in c-Jun-positive neurons 1, 7, and 14 days after surgery, but the decrease did not reach statistical significance. Conclusion : We found no significant difference in cold allodynia and the early expression of c-Fos and c-Jun between the sham and C2 resection groups. Our results may support the routine resection of the C2 nerve root for posterior C1-2 fusion, but, further studies are needed.