• Title/Summary/Keyword: Fos expression

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Pyrrolidine dithiocarbamate-induced activation of ERK and increased expression of c-Fos in mouse embryonic stem cells

  • Kim, Young-Eun;Park, Jeong-A;Nam, Ki-Hoan;Kwon, Hyung-Joo;Lee, Young-Hee
    • BMB Reports
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    • v.42 no.3
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    • pp.148-153
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    • 2009
  • Pyrrolidine dithiocarbamate (PDTC) is a stable anti-oxidant or pro-oxidant, depending on the situation, and it is widely used to inhibit the activation of NF-${\kappa}B$. We recently reported that PDTC activates the MIP-2 gene in a NF-${\kappa}B$-independent and c-Jun-dependent manner in macrophage cells. In this work, we found that PDTC activates signal transduction pathways in mouse ES cells. Among the three different mitogen-activated protein kinase (MAPK) pathways, including the extracellular-signal-regulated kinase (ERK), p38 MAP kinase, and stress-activated protein kinase (SAPK)/Jun N-terminal kinase (JNK) pathways, only the ERK pathway was significantly activated in mouse ES cells after stimulation with PDTC. Additionally, we observed a synergistic activation of ERK and induction of c-Fos after stimulation with PDTC in the presence of mouse embryonic fibroblast (MEF) conditioned medium. In contrast, another NF-${\kappa}B$ inhibitor, BMS-345541, did not activate the MAP kinase pathways or induce expression of c-Fos. These results suggest that changes in the presence of the NF-${\kappa}B$ inhibitor PDTC should be carefully considered when it used with mouse ES cells.

The Neuroprotective Effects of Uncariae Ramulus et Uncus on focal cerebral ischemia in rats brains (백서(白鼠)의 국부(局部) 뇌경색(腦硬塞)에 대한 조구등(釣鉤藤)의 신경보호(神經保護) 효과(效果))

  • Kwon Hyung-Su;Oh Yong-Seong;Lee So-Yeon;Park Chi-Sang;Park Chang-Gook;Jang Woo-Seok
    • The Journal of Internal Korean Medicine
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    • v.24 no.2
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    • pp.181-189
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    • 2003
  • The goal of this study is to investigate whether Uncariae Ramulus et Uncus can protect nerve cells against ischemic neuronal damage is caused by middle cerebral artery occlusion (MCAO) in rats' brains and to investigate whether the neuroprotective effect of Uncariae Ramulus et Uncus is concerned with IEGs(immediate early genes) expression. Uncariae Ramulus et Uncus(l00mg/kg) was administered immediately after 2 hours of MCAO and maintained for 7 days. On 7th days after 2 hours of MCAO, the brains of rats were sliced through the hippocampus. c-Fos immunohistochemistry stain and Cresyl violet stain were done for microscopic examination. Each number of viable neurons and c-Fos immunoreactive cells in CA1 was counted. The density of neurons and c-Fos immunoreactive cells were significantly decreased in MCAO-operated ischemic rats compared to that sham-operated rats. Administration of Uncariae Ramulus et Uncus group significantly elevated MCAO-induced decrease in density of neurons, and elevated MCAO-induced decrease in c-Fos immunoreactive cells. These results suggest that the neuroprotective effect of Uncariae Ramulus et Uncus against focal cerebral ischemia. Also, we hypothesized that neuroprotective mechanism of Uncariae Ramulus et Uncus is related to IEGs expression.

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Protective Effect of Polygonum Multiflorum on Cell Damage in UVB-irradiated HaCaT Keratinocytes (적하수오(赤何首烏)의 UVB로 자극한 피부 각질세포 보호 작용)

  • Lee, Seung-Ah;Yoo, Dong-Youl
    • The Journal of Korean Obstetrics and Gynecology
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    • v.24 no.4
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    • pp.31-49
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    • 2011
  • Objectives: This study was performed to assess the protective effect of Polygonum multiflorum(PM) on UVB-irradiated HaCaT Keratinocytes damage. Methods: The protective effects of Polygonum multiflorum(PM) were determined by UVB-irradiated HaCaT assay. We assessed protective effects of Polygonum multiflorum(PM) on LDH release and nitrite production from HaCaT. COX-2, Bcl-2, Bax, $TNF{\alpha}$, c-jun, c-fos, NF-${\kappa}B$, iNOS, Bcl-xL gene expression were determined in HaCaT using real-time PCR method. Results: 1. PM inhibited LDH Release in UVB-irradiated HaCaT Keratinocytes. 2. PM inhibited Nitrite Production in UVB-irradiated HaCaT Keratinocytes. 3. PM suppressed the Gene Expression of COX-2 in UVB-irradiated HaCaT Keratinocytes. 4. PM increased the Gene Expression of Bcl-2 in UVB-irradiated HaCaT Keratinocytes. 5. PM didn't increase the Gene Expression of Bax in UVB-irradiated HaCaT Keratinocytes. 6. PM suppressed the Gene Expression of $TNF{\alpha}$ in UVB-irradiated HaCaT Keratinocytes. 7. PM suppressed the Gene Expression of c-jun in UVB-irradiated HaCaT Keratinocytes. 8. PM suppressed the Gene Expression of c-fos in UVB-irradiated HaCaT Keratinocytes. 9. PM suppressed the Gene Expression of NF-${\kappa}B$ in UVB-irradiated HaCaT Keratinocytes. 10. PM suppressed the Gene Expression of i-NOS in UVB-irradiated HaCaT Keratinocytes. 11. PM didn't increase the Gene Expression of Bcl-xL in UVB-irradiated HaCaT Keratinocytes Conclusions: In conclusion, these results suggest that PM inhibited the cell damage in UVB-irradiated HaCaT.

Short-Term Cold Exposure May Cause a Local Decrease of Neuropeptide Y in the Rat Hypothalamus

  • Park, Joong Jean;Lee, Heung Kyung;Shin, Min Woo;Kim, Sung Jin;Noh, Seung Yeon;Shin, Jin;Yu, Woo Sung
    • Molecules and Cells
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    • v.23 no.1
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    • pp.88-93
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    • 2007
  • Neuropeptide Y (NPY) is an orexigenic and hypothermic peptide. To understand its role in hypothermic conditions, male rats were placed in a $24^{\circ}C$ or $4^{\circ}C$ air chamber for 1.5 h. The expression of c-Fos protein, and NPY mRNA and protein, was analyzed in the hypothalamus 1 h-2 h later. The cold treatment increased the number of c-Fos-immunoreactive cells in the paraventricular hypothalamic nucleus (PVN) and arcuate nucleus (ARC). At the same time it decreased the density of NPY-immunoreactive components in the PVN, dorsomedial hypothalamic nucleus and ARC, as well as of NPY transcripts in the PVN and ARC. No colocalization of c-Fos with NPY was detected. These results suggest that short-term cold exposure should reduce indirectly NPY production in some hypothalamic nuclei to facilitate thermogenesis without inducing feeding behavior.

Identification of GATA2 and AP-1 Activator Elements within the Enhancer VNTR Occurring in Intron 5 of the Human SIRT3 Gene

  • Bellizzi, Dina;Covello, Giuseppina;Di Cianni, Fausta;Tong, Qiang;De Benedictis, Giovanna
    • Molecules and Cells
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    • v.28 no.2
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    • pp.87-92
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    • 2009
  • Human SIRT3 gene contains an intronic VNTR enhancer. A T > C transition occurring in the second repeat of each VNTR allele implies the presence/absence of a putative GATA binding motif. A partially overlapping AP-1 site, not affected by the transition, was also identified. Aims of the present study were: 1) to verify if GATA and AP-1 sites could bind GATA2 and c-Jun/c-Fos factors, respectively; 2) to investigate whether such sites modulate the enhancer activity of the SIRT3-VNTR alleles. DAPA assay proved that GATA2 and c-Jun/c-Fos factors are able to bind the corresponding sites. Moreover, co-transfection experiments showed that the over-expression of GATA2 and c-Jun/c-Fos factors boosts the VNTR enhancer activity in an allelic-specific way. Furthermore, we established that GATA2 and c-Jun/c-Fos act additively in modulating the SIRT3-VNTR enhancer function. Therefore, GATA2 and AP-1 are functional sites and the T > C transition of the second VNTR repeat affects their activity.

Specific Isoforms of Protein Kinase G Downregulate the Transcription of Cyclin D1 in NIH3T3

  • Lim, Seon Young;Soh, Jae-Won
    • Bulletin of the Korean Chemical Society
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    • v.34 no.4
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    • pp.1165-1169
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    • 2013
  • To elucidate the role of PKG isoforms in transcriptional control of cyclin D1, we employed a series of expression vectors of PKG $1{\alpha}$ and PKG $1{\beta}$ which encode HA-tagged wild type and constitutively active (SD and ${\Delta}N$) mutants. Our present study demonstrates that both the constitutively active mutants of PKG $1{\beta}$ downregulate the transcription of cyclin D1 when transiently transfected in NIH3T3 cells, whereas PKG $1{\alpha}$ mutants show weak inhibition. We further studied the transcriptional regulators of cyclin D1, such as, c-fos, NF-${\kappa}B$, and CRE by using the luciferase reporter assay. Constitutively active mutants of PKG $1{\beta}$ showed marked transcriptional downregulation of c-fos in NIH3T3 cells, whereas PKG $1{\alpha}$ downregulated c-fos to a lesser extent. We also found that the constitutively active mutants of PKG negatively regulated the activation of NF-${\kappa}B$ and CRE, suggesting their involvement in the regulation of cyclin D1.

Pharmacological Action of Radix Scutellariae on Nicotine-Induced Locomotor Activity and C-Fos Expression in Rats. (황금의 니코틴 약물투여에 의한 유전자 발현과 행동적 변동에 미치는 약리작용)

  • Lee Bom-Bi;Chae Youn-Byoung;Kwon Young-Kyu;Yang Chae-Ha;Kim Mi-Ryeo;Kim Kwang-Jung;Seo Yong-Min;Kim Jang-Hyun;Hahm Dae-Hyun;Lee Hye-Jung;Pyun Kwang-Ho;Shim In-Sop
    • The Journal of Korean Medicine
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    • v.26 no.3 s.63
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    • pp.1-12
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    • 2005
  • Objectives : Substantial evidence suggests that reinforcing effects of nicotine can be mediated by the mesolimbic dopaminergic system. It has been shown that repeated injections of nicotine produce an increase in locomotor activity and expression of the immediate-early gene, c-fos, in the dopaminergic target areas. Herbal medicine as a therapeutic intervention has been widely used for the treatment of mental dysfunction. Many studies have shown that Radix Scutellariae (RS) can affect the biochemical balance in the central nervous system. Tn order to investigate whether RS has an influence on nicotine-induced behavioral sensitization, we examined the effect of RS on nicotine-induced locomotor activity and c-fos expression in the striatum and nucleus accumbens utilizing the fos-tike immunohistochemistry (FLI). Methods : Male SD rats received RS (200mg/kg, i.p.) 30min before repeated daily injections of nicotine (0.4mg/kg, s.c.) for 7 days. This was followed by withdrawal for 3 days and one challenge for 1 day. Results : System challenge with nicotine produced a much larger increase in locomotor activity and accumbal FLI. Pretreatment with RS significantly inhibited nicotine-induced locomotor activity and FLI in the striatum and nucleus accumbens. Conclusions : These results demonstrate that reduction in locomotor activity by RS may be reflected by reduction of dopamine release and postsynaptic neuronal activity in the striatum and nucleus accumbens. Our results suggest that RS may have therapeutic effect on nicotine addiction.

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Effect of Herbal-Acupuncture on Repeated Cocaine-induced Behavioral Sensitization in the Rat (약침이 반복적인 코카인 투여로 인한 행동적 민감화 현상에 미치는 효과)

  • Lee, B.B;Yang, C.H.;Hahm, D.H.;Lee, H.J.;Shim, I.S.
    • Journal of Pharmacopuncture
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    • v.7 no.1 s.12
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    • pp.53-61
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    • 2004
  • Substantial evidence suggests that behavioral and reinforcing effects of cocaine can be mediated by the mesolimbic dopaminergic system. It has been shown that repeated injections of cocaine produce increase in locomotor activity, expression of the immediate-early gene, c-fos in the nucleus accumbens (NAc), which was one of the main dopaminergic terminal areas. Herbal-acupuncture as a therapeutic intervention has been widely used for the treatment of many functional disorders such as drug abuse. Coptidis Rhizoma (CR) and its main component, berberine (BER) were selected as herbal medicine of herbal-acupuncture. Both medicines have been known to have the therapeutic effect on the central nervous system. In order to investigate the effects of CR and BER herbalacupuncture at shenmen (HT7) point (CR/H and BER/H) on the cocaine-induced behavioral sensitization, the influence of CR/H and BER/H on repeated cocaine-induced locomotor activity, the change of c-Fos expression in the brain by immunohistochemistry were examined. Male SD rats were given CR/H (0.4mg/kg) and BER/H (0.1mg/kg) 30 min before daily injections of cocaine hydrochloride (15mg/kg. i.p.) 10 days. After 3 days withdrawal, rats received a challenge injection of cocaine (15mg/kg, i.p.). Systemic challenge with cocaine produced much larger increased locomotor activity, accumbal Fos-like immunoreactivity in the NAc. Pretreatment with CR/H and BER/H significantly inhibited cocaine-induced locomotor activity, the change of c-Fos expression in the rats. Our data demonstrated that the inhibitory effects of cocaine-induced behavioral sensitization by CR/H and BER/H were closely associated with the reduction of presynaptic dopamine release in the NAc. These results suggest that CR/H and BER/H can be effectively applied to cocaine addiction.

Inhibitory Effect of Amygdalin on Lipopolysaccharide-Inducible TNF-$\alpha$ and IL-l$\beta$ mRNA Expression and Carrageenan-Induced Rat Arthritis

  • Hwang, Hye-Jeong;Lee, Hye-Jung;Kim, Chang-Ju;Shim, In-Sop;Hahm, Dae-Hyun
    • Journal of Microbiology and Biotechnology
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    • v.18 no.10
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    • pp.1641-1647
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    • 2008
  • Amygdalin is a cyanogenic glycoside plant compound found in the seeds of rosaceous stone fruits. We evaluated the anti-inflammatory and analgesic activities of amygdalin, using an in vitro lipopolysaccharide (LPS)-induced cell line and a rat model with carrageenan-induced ankle arthritis. One mM amygdalin significantly inhibited the expression of TNF-$\alpha$ and IL-l$\beta$ mRNAs in LPS-treated RAW 264.7 cells. Amygdalin (0.005, 0.05, and 0.1 mg/kg) was intramuscularly injected immediately after the induction of carrageenan-induced arthritic pain in rats, and the anti-arthritic effect of amygdalin was assessed by measuring the weight distribution ratio of the bearing forces of both feet and the ankle circumference, and by analyzing the expression levels of three molecular markers of pain and inflammation (c-Fos, TNF-$\alpha$, and IL-l$\beta$) in the spinal cord. The hyperalgesia of the arthritic ankle was alleviated most significantly by the injection of 0.005 mg/kg amygdalin. At this dosage, the expressions of c-Fos, TNF-$\alpha$, and IL-l$\beta$ in the spinal cord were significantly inhibited. However, at dosage greater than 0.005 mg/kg, the pain-relieving effect of amygdalin was not observed. Thus, amygdalin treatment effectively alleviated responses to LPS-treatment in RAW 264.7 cells and carrageenan-induced arthritis in rats, and may serve as an analgesic for relieving inflammatory pain.