• BMB Reports
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• v.55 no.8
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• pp.389-394
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• 2022

In particular, the phenomenon of c-Jun degradation within the inflammatory response has not yet been fully analyzed. In order to verify this, we investigated LPS-stimulated murine macrophages pre-treated with sodium orthovanadate (SO) in order to uncover the regulatory mechanisms of the MAPKs which regulate c-Jun degradation within the inflammatory response. Through our study, we found that SO suppressed the production of prostaglandin E₂ (PGE₂) and the expression of COX-2 in LPS-stimulated RAW264.7 cells. Additionally, SO decreased total c-Jun levels, without altering the amount of mRNA, although the phospho-levels of p38, ERK, and JNK were strongly enhanced. Through the usage of selective MAPK inhibitors, and knockdown and overexpression strategies, p38 was revealed to be a major MAPK which regulates c-Jun degradation. Further analysis indicates that the phosphorylation of p38 is a determinant for c-Jun degradation, and is sufficient to induce ubiquitination-dependent c-Jun degradation, recovered through MG132 treatment. Therefore, our results suggest that the hyperphosphorylation of p38 by SO contributes to c-Jun degradation, which is linked to the suppression of PGE₂ secretion in inflammatory responses; and thus, finding drugs to increase p38 activity could be a novel strategy for the development of anti-inflammatory drugs.

• Archives of Pharmacal Research
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• v.27 no.4
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• pp.396-401
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• 2004

The effects of lipopolysaccharide (LPS) and several cytokines or the c-fos and c-jun mRNA expression were examined in primary cultured astrocytes. Either LPS (500 ng/mL) or inter-feron-$\gamma$ (IFN-$\gamma$ 5 ng/mL) alone increased the level of c-fos mRNA (1 h). However, tumor necro-sis factor-$\alpha$ (TNF-$\alpha$; 10 ng/mL) or interleukin-4 (IL-1$\beta$: 5 ng/mL) alone showed no significant induction of the level of c-fos mRNA. TNF-$\alpha$ showed a potentiating effect in the regulation of LPS-induced c-fos mRNA expression, whereas LPS showed an inhibitory action against IFN-Y-induced c-fos mRNA expression. LPS, but not TNF-$\alpha$, IL-1$\beta$ and IFN-$\gamma$, increased the level of c-jun mRNA (1 h). TNF-$\alpha$ and IFN-$\gamma$ showed an inhibitory action against LPS-induced c-jun mRNA expression. Both phorbol 12-myristate 13-acetate (PMA; 2.5 mM) and forskolin (FSK, 5 mM) increased the c-fos and c-jun mRNA expressions. In addition, the level of c-fos mRNA was expressed in an antagonistic manner when LPS was combined with PMA. When LPS was co-treated with either PMA or FSK, it showed an additive interaction for the induction of c-jun mRNA expression. Our results suggest that LPS and cytokines may be actively involved in the regulation of c-fos and c-jun mRNA expressions in primary cultured astrocytes. Moreover, both the PKA and PKC pathways may regulate the LPS-induced c-fos and c-jun mRNA expressions in different ways.

• Journal of the Korean Society of Food Science and Nutrition
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• v.25 no.6
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• pp.1024-1030
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• 1996

Capsaicin (8-methyl-N-vanillyl-6-nonenamide: CAP) is a mai or ingredient of hot pepper that has been used as a spicy food additive, preservative, and medicine. In this study, we evaluated the effect of dietary CAP on the selected proto-oncogene(c-jun, c-myc, H-ras, erbB, p53) expressions in various tissues of mice. Male ICR mice were divided into four groups and fed the experimental diets containing CAP at the levels of 0, 5, 20 and 100ppm for four weeks. Steady state RNA levels in various tissues were measured by slot blot hybridization assay. C-jun expression level was enhanced in stomach tissue from mice fed 20ppm CAP and significantly reduced from mice fed 100ppm CAP. The c-jun expression levels were differentially altered in organ-specific manner, Tumor suppressor gene p53 expression level appeared to be slightly increased in the liver from mice fed 20ppm CAP. These results suggested that dietary CAP differentially modulates c-jun and p53 expression in various organs.

• The Korean Journal of Physiology and Pharmacology
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• v.5 no.1
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• pp.19-25
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• 2001

We have studied the effects of excitatory amino acids on the expression of the c-fos and c-jun mRNA in rat C6 glioma cells. The glutamate, $N-methyl-_D-aspartate$ (NMDA), and kainic acid (KA) increased c-fos mRNA level in a concentration-dependent manner. However, they did not affect c-jun mRNA level. In addition, forskolin and phorbol 12-myristate 13-acetate (PMA) increased c-fos mRNA level. Furthermore, PMA increased c-jun mRNA level whereas forskolin downregulated c-jun mRNA level. The glutamate, NMDA and KA, at a concentration of 0.25 mM, did not affect the basal c-fos and c-jun mRNA levels, and also did not affect forskolin- and PMA-induced responses. Furthermore, both forskolin and PMA itself increased the phosphorylation of ERK (extracellular signal regulated kinase) and CREB (cyclicAMP responsible element binding protein) proteins. The KA, NMDA, and glutamate did not affect forskolin- induced increase of ERK and CREB phosphorylation. The KA decreased PMA-induced increase of phosphorylation of ERK and CREB proteins, whereas glutamate and NMDA did not affect the phosphorylation of ERK and CREB proteins induced by PMA. These findings suggest that, in C6 glioma cells, c-fos mRNA induction induced by EAAs is not mediated by phosphorylation of ERK and CREB proteins.

• 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.

• The Journal of Internal Korean Medicine
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• v.26 no.3
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• pp.533-542
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• 2005

Objectives : In this study, aged BCAO rats were used to observe the effect of Bupleuri Radix on brain ischemic injury because aging is an important factor in storke. Methods : The brain ischemic injury was induced by temporary closing carotids on both sides in a low blood pressure state, and Bupleuri Radix was orally administered to 18 month-old BCAO rats. The ischemic damaged hippocampus and c-Fos and c-Jun expression were analyzed by the immunohistochemical staining. Result and Conclusions : Results are summarized as fellows; 1. The c-Fos expression after inducing a brain ischemic injury in the hippocampus was more inhibited in the experimental group than in the control group. 2. The normalized optical density of c-Fos expression was more reduced in cornu ammonis(CA)1, dentate gyrus(DG) areas in the experimental group than in the control group. 3. The c-Jun expression after inducing a brain ischemic injury in the hippocampus was more inhibited in the experimental group than in the control group. 4. The normalized optical density of c-Jun expression was more reduced in CA1 and DG areas in the experimental group than in the control group.

• The Journal of Internal Korean Medicine
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• v.25 no.3
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• pp.473-481
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• 2004

Objective : In this study old BCAO rats were observed for effects of 'Dea-Hwang' on brain ischema injury, because risk of stroke increases with age. Method : The brain ischema injury was induced by temporarily closing carotids on both sides in a low blood pressuer state and Dea-Hwang was administered orally to 18 month-old BCAO rats. Results and Conclusions : The ischemically damaged Hippocampus and c-fos and c-jun expression were analyzed by immunohistochemical staining and results are summarized as follows: 1. The c-fos expression after inducing a brain ischema injury in the hippocampus was more inhibited in the dosed group than in the control group. 2. The normalized optical density of c-fos expression was more reduced in the CA1, CA2, and DG areas of the dosed group than in those of the control group. 3. The c-jun expression after inducing brain ischema injury in the hippocampus was more inhibited in the dosed group than in the control group. 4. The normalized optical density of c-jun expression was more reduced in the CAI area of the dosed group than in that of the control group.

• The Journal of Korean Society of Virology
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• v.28 no.3
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• pp.267-274
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• 1998

Human cytomegalovirus (HCMV) has the ability to activate the expression of many viral and cellular genes. Among various viral proteins, the immediate early proteins (IE1-72kDa, IE2-86kDa) have been known to be potent transactivators. The product of c-jun proto-oncogene is important in cell activation and differentiation. Here, we tried to find out if the IE could activate the c-jun promoter and also tried to identify the responsible sequence elements in the c-jun activation by IE1-72kDa. We found HCMV IE expression transactivated the c-jun promoter in human embryonal lung fibroblasts (HEL). The activation fold by IE1-72kDa, IE2-86kDa and IE2-55kDa was 23, 35, and 5, respectively. When the expression of each IE was combined, it showed synergism. Expression of (IE1-72kDa + IE2-86kDa) and (IE1-72kDa + IE2-86kDa + IE2-55kDa) resulted in 131 and 162 fold increase, respectively. The c-jun promoter region between -117 and -59 contains binding sites for the transcription factors Spl, CAAT, AP-l like (ATF/CREB), and MEF2. Transient expression assays were performed using various reporter plasmids containing the c-jun promoter-regulatory region linked to the luciferase gene and a plasmid expressing HCMV IE1 gene. Deletional and point mutational analysis showed that the sequence between -225 to -160 and the CTF binding site were involved in the up-regulation of c-jun promoter.

• Radiation Oncology Journal
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• v.17 no.3
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• pp.223-229
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• 1999

Purpose : The expression pattern of c-jun by ionizing radiation according to cell growth state (exponential growth vs. stationary phase) and its relationship with cell cycle redistribution were investigated. Materials and Methods : The exponential growth phase (day 4) and stationary phase (day 9) cells were determined from cell growth curve according to the elapse of days in CaSki. The cells were irradiated using 6 MV X-ray with a dose of 2 Gy at a fixed dose rate of 3 Gy/min. Northern blot analysis was peformed with total cellular RNA and cell cycle distribution was analyzed using flow cytometry according to time-course after irradiation. Results : The maximum expression of c-jun occurred 1 hour after irradiation in both exponential growth and stationary phase cells. After then c-jun expression was elevated upto 6 hours in exponential growth phase cells, but the level decreased in stationary phase cells. Movements of cells from G0-G1 to S, G2-M phase after irradiation were higher in exponential growth phase than stationary phase. Conclusion : c-jun may be involved in the regulation of cellular proliferation according to the growth states after irradiation.

• The Journal of Internal Korean Medicine
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• v.24 no.2
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• pp.337-347
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• 2003

This study investigated the effect of Yanggyuksanhwa-tang on cerebral ischemia of the rats. Considering age-related impact on cerebral ischemia, aged rats (18 months old) were used for this study. Ischemic damage was induced by the transient occlusion of bilateral common carotid arteries(BCAO) under the hypotension. Yanggyuksanhwa-tang was administered twice orally. Then changes of immunohistochemical expression of c-fos and c-jun in ischemic damaged hippocampus were observed. The BCAO in aged rats led significant increase of c-fos expression in CA1 and DG of hippocampus. While the treatment of Yanggyuksanhwa-tang significantly attenuated the increase of c-fos expression in CA1 hippocampus following BCAO ischemia. Depending on changes of the normalized optical density(NOD) of immunohistochemical c-fos expression, the treatment of Yanggyuksanhwa-tang significantly attenuated the increase of NOD in CA1 and DG of hippocampus. And there was not changes in CA2 and CA3 hippocampus with respect to the control BCAO group. The BCAO in aged rats led significant increase of c-jun expression in CA1 hippocampus. While the treatment of Yanggyuksanhwa-tang significantly attenuated the increase of c-jun expression in CA1 hippocampus following BCAO ischemia. Depending on changes of the NOD of immunohistochemical c-jun expression, the treatment of Yanggyuksanhwa-tang significantly attenuated the increase of NOD in CA1 hippocampus. And there was not changes in CA2, CA3 and DG of hippocampus with respect to the control BCAO group.