• Molecular & Cellular Toxicology
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• v.1 no.1
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• pp.52-61
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• 2005

Transcript profiling is a particularly valuable tool in the field of steroid receptor biology, as these receptors are ligand-activated transcription factors and therefore exert their initial effects through altering gene expression in responsive cells. Also, an awareness of endocrine disrupting chemicals (EDCs) and their potential screening methods to identify endocrine activity have been increased. Here we developed an in-house cDNA microarray, named KISTCHIP-400 ver. 1.0, with 416 clones, based on public database and research papers. These clones contained estrogen, androgen, thyroid hormone & receptors, sex hormone signal transduction & regulation, c-fos, c-myc, ps2 gene, metabolism related genes etc. Also, to validate the KISTCHIP-400 ver. 1.0, we investigated gene expression profiles with reference hormones, $10^{8}\;M\;17{\beta}-estradiol,\;10^{-7}\;M\;testosterone\;and\;10^{-7}\;M$ progesterone in MCF-7 cell line. As the results, gene expression profiles of three reference hormones were distinguished from each other with significant and identified 33 $17{\beta}-estradiol$ responsive genes. This study is in first step of validation for KISTCHIP-400 ver. 1.0, as following step transcriptional profile analysis on not only low concentrations of EDCs but suspected EDCs using KISTCHIP-400 ver. 1.0 is processing. Our results indicate that the developed microarray may be a useful laboratory tool for screening EDCs and elucidating endocrine disrupting mechanism.

• 한국생물공학회:학술대회논문집
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• 2000.11a
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• pp.208-211
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• 2000

The recombinant fluorescent chinese hamster ovary (CHO) cell line was developed and optimized through this study for biomonitoring system. This cell line, called KFC-A10, contains recombinant plasmid(pKCFG) constructed in this study for detecting toxic conditions (Mitomicyn C, EDCs, ${\gamma}-ray$, etc.). It is known that c-Fos is involved in proliferation and differentiation of the signal transduction and overexpression of this gene can lead cell to death under the toxic conditions including apoptosis status. Therefore, pKCFG which has the c-fosSRE::GFP is induced by toxic chemicals, especially DNA damage agents and apoptotic chemicals, and produces green fluorescence protein(GFP) under these toxic conditions. Through the characterization of KFC-A10 using fluorescent assays of GFP, it was shown that KFC-A10 cell line had a manifest GFP expression pattern due to various toxicants especially mitomycin C, ${\gamma}-ray$ and bisphenol A. Therefore this study proved the possibility of using GFP as a reporter for detecting various toxicants

• BMB Reports
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• v.40 no.4
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• pp.475-485
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• 2007

Methamphetamine is an illicit drug that is often abused and can cause neuropsychiatric and neurotoxic damage. Repeated administration of psychostimulants such as methamphetamine induces a behavioral sensitization. According to a previous study, Bax was involved in neurotoxicity by methamphetamine, but the function of Bax in rewarding effect has not yet been elucidated. Therefore, we have studied the function of Bax in a rewarding effect model. In the present study, we treated chronic methamphetamine exposure in a Bax-deficient mouse model and examined behavioral change using a conditioned place preference (CPP) test. The CPP score in Bax knockout mice was decreased compared to that of wild-type mice. Therefore, we screened for Bax-related genes that are involved in rewarding effect using microarray technology. In order to confirm microarray data, we applied the RT-PCR method to observe relative changes of Bcl2, a pro-apoptotic family gene. As a result, using our experiment microarray, we selected genes that were associated with Bax in microarray data, and eventually selected the Tgfbr2 gene. Expression of the Tgfbr2 gene was decreased by methamphetamine in Bax knockout mice, and the gene was overexpressed in Bax wild-type mice. Additionally, we confirmed that Creb, FosB, and c-Fos were related to rewarding effect and Bax using immunohistochemistry.

• 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.

• Journal of Sasang Constitutional Medicine
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• v.11 no.2
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• pp.283-299
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• 1999

1. Purpose : Systemic injection of kainic acid in experimental animals induces the limbic seizure and structural damages in hippocampus and amygdala which resembles the changes in human temporal lobe epilepsy. The author performed this study to investigate the neuroprotective effects of Yuldahansotang, on the neurotoxicity induced by kainic acid in the hippocampus in rats. 2. Method : Kainic acid was administered intraperitoneally. And feeding with Yuldahansotang for 3 weeks after kainic acid administration. Seizure were induced in male mice (kainate 10-40 mg/kg i.p) and animals were sacrified at various time-points after injection. The experimental animals were sacrificed at 1, 2, 3day and 1, 3weeks while Yuldahansotang administrations. Seizure were graded using a behavioral scale developed in our laboratory. c-fos belong to immediate early genes(IEGs) known to have rapid and brief responses. And neuronal injury was assayed by examining DNA fragmentation using in situ nick translation histochemistry. 3. Results & Conclusion : Seizure severity paralled kainate dosage. At higher doses DNA fragmentation is seen mainly in hippocampus in area CA3, and variable in CA1, thalamus, amygdala within 24 h, is maximal within 72 h, and is large gene by 7 days after administration of kainate. And we can't see the expression of DNA fragmentation and c-fos in the mice what feeded by Yuldahansotang after 7 days from kainic acid administration. It is consequently suggested that Yuldahansotang may attenuate the kainic acid-induced neuronal degeneration and increase the immunoreactivity of hippocampus in mouse.

• 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.

• Proceedings of the Korea Society of Environmental Toocicology Conference
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• 2003.05a
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• pp.180-180
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• 2003

Transcript profiling is a particularly valuable tool in the field of steroid receptor biology, as these receptors are ligand-activated transcription factors and therefore exert their initial effects through altering gene expression in responsive cells. Also, an increased awareness of endocrine disrupting chemicals (EBCs) and their potential to affect wildlife and humans has produced a demand for practical screening methods to identify endocrine activity. Here we developed an in-house cDNA microarray, named KISTCHIP-400, with 401 clones, hormone related genes, factors, and ESTs, based on public database and research papers. Theses clones contained estrogen, androgen, thyroid hormone St receptors, sex hormone signal transduction ＆ regulation, c-fos, c-myc, ps2 gene, metabolism related genes etc. And to validate the KISTCHIP-400, we investigated gene expression profiles with reference hormones, 10$\^$-8/ M 17be1a-estradiol, 10$\^$-7/ M testosterone, 10$\^$-7/ M progesterone, and thyroxin in MCF-7 cell line. Although it is in first step of validation, low doses and combinations of EDCs need to be tested. Our preliminary results that indicate the developed microarray may be a useful laboratory tool for screening EDCs and elucidating endocrine disrupting mechanism.

• Journal of Physiology & Pathology in Korean Medicine
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• v.25 no.1
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• pp.109-114
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• 2011

Atractylodis Rhizoma Alba is commonly used herbal medicine and it has been known that has immuno-regualtory effects and anti-cancer effects. The inhibition of osteoclastogenesis is essential for the prevention and treatment of osteoporosis. The aim of this study was to evaluate the effects of Atractylodis Rhizoma Alba on osteoclast differentiation in vitro and on resorbing activity of osteoclast. Osteoclast formation was evaluated in bone marrow cells (BMC) in the presence or absence of Atractylodis Rhizoma Alba. The expression of c-fos, tartrate-resistant acid phosphatase (TRAP), OSCAR, DC-STAMP, cathepsin K, MafB and NFATc1 mRNA in osteoclast precursor were assessed by RT-PCR. The levels of TNF receptor-associated factor-6 (TRAF-6), c-fos and NFATc1 protein were assessed by Western blot analysis. Also the correlation with MAPKs and NF-${\kappa}B$ pathways were measured by using Western blot analysis. With bone resorption study, I tried to evaluate the inhibitory effects of Atractylodis Rhizoma Alba on mature osteoclast function. Atractylodis Rhizoma Alba inhibited the RANKL induced osteoclastic differentiation from bone marrow macrophage in a dose dependant manner without cellular toxicity. Gene expression of c-fos and NFATc1 was significantly down regulated with Atractylodis Rhizoma Alba treatment. Atractylodis Rhizoma Alba markedly inhibited the RANKL-induced osteoclastogenesis through suppression of nuclear factor kappa b (NF-${\kappa}B$) pathway, down stream pathway of p38, ERK and JNK pathway. Taken together, I concluded that Atractylodis Rhizoma Alba have beneficial effect on osteoporosis by inhibition of osteoclast differentiation and by inhibition of functioning osteoclast. Thus I expect that Atractylodis Rhizoma Alba could be a treatment option for osteoporosis.

• Food Science and Biotechnology
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• v.17 no.4
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• pp.713-717
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• 2008

In the present study, chronic effects of the hot water extracts of walnut seed (Juglans regia L.) (WSE) and Nelumbo nucifera seed (NSE) were investigated in mice exposed to 2 hr of restraint stress each day for 4 weeks. Corticosterone levels in serum were significantly increased in the vehicle-treated stressed group ($25\;{\mu}g/dL$) compared to that in the control group ($13\;{\mu}g/dL$). This stress induced gastric redness and lesions. However, treatment with WSE and/or NSE significantly protected the stomach from this lesion by 50-60% compared to that in the vehicletreated group. In the amygdala, the administration of WSE and/or NSE also reduced the immediate early gene (c-fos) expression by 70-90% vs. the vehicle-treated group. These suggest that WSE and/or NSE may reduce the appearance of symptoms induced by stress and these materials are useful as anti-stress foods, as natural products tend to be relatively safe compared to chemical products.

• Proceedings of the PSK Conference
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• 2000.10a
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• pp.206.2-206.2
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• 2000